Full HSR proceedings Vol. 4

Transcript

• Xenon and cerebral oxygen saturation
• A survey on prophylactic intraaortic balloon counterpulsation
• ECMO “stand-by” for cesarean section
• Multiple sclerosis and off-pump coronary surgery
• Cardiac manifestations of subarachnoid hemorrhage
• Dexmedetomidine and postoperative sedation after cardiac surgery
• Imaging in cardiovascular medicine
• Papers, Posters, Presentations: communicating the biomedical sciences
IN THE NEXT ISSUES
Vol. 4 · N° 4
· 2012
Alberto Zangrillo
Roland Hetzer
Editors
Intensive Care
Cardiovascular Anesthesia
in
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proceedings
ISSN: 2037-0504
ASSOCIATE EDITORS
Luciano Gattinoni
Università degli Studi di Milano, Policlinico di Milano, Italia
Massimo Antonelli
Università Cattolica Sacro Cuore, Policlinico Gemelli, Roma, Italia
Antonio Pesenti
Università degli Studi di Milano Bicocca, Ospedale San Gerardo, Italia
Giovanni Landoni
Università Vita-Salute San Raffaele, Milano, Italia
Vol. 4 • N° 4 • 2012
Marco Ranieri
Università di Torino S. Giovanni Battista Molinette, Torino, Italia
EDITORS IN CHIEF
Alberto Zangrillo
Università Vita-Salute San Raffaele
Milano, Italia
SECTION EDITORS
! INTENSIVE CARE
Luciano Gattinoni
Università degli Studi di Milano, Policlinico di Milano, Italia
! ANESTHESIA
Roland Hetzer
Deutsches Herzzentrum Berlin, Germany
Fabio Guarracino
Azienda Ospedaliera Universitaria Pisana, Pisa, Italia
! VASCULAR SURGERY
Roberto Chiesa
Official Journal of
School of Anesthesiology
and Intensive Care
Milano, Italia
! CARDIAC SURGERY
Ottavio Alfieri
! PEDIATRIC CARDIAC SURGERY
AND CONGENITAL HEART DISEASES
Eva Maria Javier Delmo Walter
Endorsed by
ITACTA
(Italian Association
of Cardiothoracic Anaesthesiologists)
www.itacta.org
Children‘s Hospital and Harvard Medical School, Boston, MS, USA;
! CARDIOLOGY
Giuseppe Biondi-Zoccai
Università degli Studi “La Sapienza”, Roma, Italia
! PEDIATRIC CARDIOLOGY
Brigitte Stiller
Universitaetsklinikum Freiburg, Germany
! ECHOCARDIOGRAPHY
Michele Oppizzi
Editor
! NEW TECHNOLOGIES
Federico Pappalardo
! IN HOSPITAL EMERGENCIES
Luca Cabrini
! PEER-TO-PEER COMMUNICATION
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Michael John
! IMAGING
Antonio Grimaldi
! FUTURE EVENTS
George Silvay
The Mount Sinai School of Medicine, New York, NY
EDITORS
Rinaldo Bellomo
Austin Hospital, Melbourne, Australia
Friedhelm Beyersdorf
Universitätsklinikum Freiburg, Freiburg,
Germany
Editorial Secretariat
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Anesthesia and Intensive Care
Università Vita-Salute San Raffaele, Milano
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Carlos Mestres
Hospital Clínico, University of Barcelona,
Barcelona, Spain
Università Vita-Salute San Raffaele,
Milano, Italia
Julije Mestrovic
Tiziana Bove
Milano, Italia
Maria Grazia Calabrò
Milano, Italia
Enrico Camporesi
University of South Florida, Tampa,
Florida
Fortis Hospitals, Bangalore, India
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Andrea Morelli
Università degli Studi “La Sapienza”,
Roma, Italia
Daniela Pasero
Ospedale San Giovanni Battista, Torino,
Italia
Laura Pasin
Milano, Italia
Gianluca Paternoster
A.O.R. Ospedale San Carlo, Potenza, Italia
Emanuele Piraccini
Ospedale “G.B. Morgagni-Pierantoni”,
Forlì, Italia
Jose Luis Pomar
Hospital Clínico, University of Barcelona,
Barcelona, Spain
Città di Lecce Hospital, GVM Care
& Research, Lecce, Italia
Martin Ponschab
Remo Daniel Covello
J. Scott Rankin
Milano, Italia
Vanderbilt University, Nashville, Tennessee,
USA
Michele De Bonis
Marco Ranucci
Milano, Italia
IRCCS Policlinico San Donato, Milano,
Italia
Paolo Del Sarto
Zaccaria Ricci
Ospedale del Cuore, FTGM, Massa, Italia
Francesco De Simone
Milano, Italia
Juergen Ennker
Mediclin Heart Institute, Lahr, Germany
Gabriele Finco
Università di Cagliari, Cagliari, Italia
Editor
Kevin Lobdell
Giovanni Borghi
Director in chief
The Journal is indexed in
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ISSN (ONLINE): 2037-0512
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France
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Massimo Clementi
Registered at the Milan Tribunal
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Gian Franco Gensini
Trauma Hospital Linz, Linz, Austria
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Reitze N. Rodseth
Nelson R. Mandela School of Medicine,
University of KwaZulu-Natal, Durban,
South Africa
Stefano Romagnoli
Ospedale Careggi, Firenze, Italia
Laura Ruggeri
Università degli Studi di Firenze, Italia
Milano, Italia
Ravi Gill
Luca Severi
University Hospital Southampton NHS
Foundation Trust, Southampton, UK
Azienda Ospedaliera San Camillo
Forlanini, Roma, Italia
Massimiliano Greco
Andrea Szekely
Milano, Italia
Semmelweis University, Budapest, Hungary
James L. Januzzi
Milano, Italia
Harvard University, Massachusetts
General Hospital, US
Marian Kuckucka
Anna Mara Scandroglio
Luigi Tritapepe
Università degli Studi “La Sapienza”,
Roma, Italia
Chiara Lazzeri
Emiliano Vitalini
Azienda Ospedaliero-Universitaria
Careggi, Firenze, Italia
Ospedale San Camillo Forlanini, Roma,
Italia
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CONTENTS
! EDITORIAL
State of the art in cardiothoracic surgery: now and in the next decade .......................................... 209
E.M. Delmo Walter, R. Hetzer
! EXPERT OPINION
State of the art in cardiovascular perfusion: now and in the next decade .................................. 211
F. Merkle, B. Haupt, A. El-Essawi, R. Hetzer
Coronary artery surgery: now and in the next decade
.......................................................................................................
217
J.C. Ennker, I.C. Ennker
Clinical results of implanted tissue engineered heart valves
................................................................................
225
P.M. Dohmen
Management of sterno-mediastinitis ....................................................................................................................................................................... 233
I.C. Ennker, J.C. Ennker
........................................................
243
.....................................................................................................................................................
251
Acute and chronic thoracic aortic disease: surgical considerations
M. Loebe, D. Ren, L. Rodriguez, S. La Francesca, J. Bismuth, A. Lumsden
! ORIGINAL ARTICLE
Cardiovascular tissue banking in Europe
T.M.M.H. de By, R. Parker, E.M. Delmo Walter, R. Hetzer
Tricuspid valve surgery ....................................................................................................................................................................................................................... 261
C.A. Mestres, G. Fita, V.M. Parra, J.L. Pomar, J.M. Bernal
! IMAGES IN MEDICINE
Is flow really continuous in last generation continuous
flow Ventricular Assist Devices? A comparison between HeartMate II
and HeartWare HVAD ............................................................................................................................................................................................................................ 268
G. Melisurgo, M. De Bonis, M. Pieri, T. Nisi, S. Silvetti, A. Zangrillo, F. Pappalardo
! LETTER TO THE EDITOR .......................................................................................................................................................................................................... 271
! PAPERS, POSTERS, PRESENTATIONS: COMMUNICATING
THE BIOMEDICAL SCIENCES
Wish you were here!..................................................................................................................................................................................................................................... 274
M. John
207
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Editorial
HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4(4): 209-210
State of the art in cardiothoracic
surgery: now and in the next decade
Deutsches Herzzentrum Berlin, Berlin, Germany
In pursuance of one of its objectives, the Roland Hetzer International Cardiothoracic and Vascular Surgery (RHICS), held its 3rd
Expert Forum on May 25th 2012 in Shanghai, China. The Chinese
colleagues, who have spent some time at the Deutsches Herzzentrum Berlin for their specialty training have been very enthusiastic in inviting the Society, which coincided with the 6th Oriental
Congress of Cardiology and the 1st Sino-German Forum on Cardiac
Surgery. This was indeed a great Meeting, with an overwhelming
8000 participants.
The Meeting has been an excellent avenue to foster and strengthen
international and professional relationships. This is a modern approach to education for the cardiothoracic physicians, adult or pediatric, interested in its scope. The session was called the “State of the
art in cardiothoracic surgery: now and in the next decade”, which
is a potpourri of various interesting subjects ranging from surgical
options in heart failure, surgery of ischemic heart, congenital heart
disease surgery, heart and lung transplantation, tissue engineering,
cardiovascular anesthesia and perfusion, cardiothoracic imaging,
hybrid and robotic surgery, and tissue banking.
This has been intentionally chosen this way, as highly diverse,
so we can bring the European and North American experiences
on these fields across the Pacific, discussing what is actually happening in these fields and sharing the visions for the future. This
has been very successful, and has been well-received by the Asian
community. We wish to thank all our Chinese friends who let this
happen.
Some of the presentations in this forum have been submitted as
Corresponding author:
Eva Maria Delmo Walter
Deutsches Herzzentrum Berlin
Augustenburger Platz 1
13353 Berlin, Germany
e-mail: [email protected]
HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012, Vol. 4
209
210
manuscripts, and seven of them, i.e. coronary artery surgery, surgery for mediastinitis, tricuspid valve surgery, aortic surgery, tissue engineering, perfusion and tissue banking, appeared in this
issue of “HSR Proceedings in Intensive Care and Cardiovascular
Anesthesia”. We are really very grateful to our dear Italian friends,
Prof. Zangrillo and Dr. Landoni, for facilitating the publication of
the RHICS Expert Forum manuscripts, in an excellent scientific
quality of high international standard.
The Pubmed indexing of the Journal is timely, since everything
that has been published, in the last few years, and that will be published in the future, is equal to, and maybe even better than some
papers published in other prestigious journals. We wish the HSR
Proceedings in Intensive Care and Cardiovascular Anesthesia and
the RHICS more success in future undertakings.
Cite this article as: Delmo Walter EM, Hetzer R. State of the art in cardiothoracic surgery: now and in the next decade. HSR
Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4 (4): 209-210
Source of Support: Nil. Conflict of interest: None declared.
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EXPERT OPINION
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State of the art in cardiovascular
perfusion: now and in the next decade
F. Merkle1,2, B. Haupt2,3, A. El-Essawi3, R. Hetzer4
1
Academy for Perfusion, Deutsches Herzzentrum Berlin, Germany; 2Steinbeis Transfer Instutite Kardiotechnik, Berlin, Germany;
Department of Cardiac Surgery, Klinikum Braunschweig, Germany; 4Department of Cardiac Surgery, Deutsches Herzzentrum
Berlin, Germany
3
ABSTRACT
The development and improvement of cardiopulmonary bypass technology is an ongoing process. During the
past decade, a number of publications on improvements and best practices have appeared, especially in the
areas of biocompatibility, materials sciences, instrumentation, monitoring of physiological parameters and
knowledge base (education and evidence-based medicine). Biocompatibility may be defined not only as an
inherent property of a particular composition of matter, but also as a set of properties concerning shape, finish,
fabrication techniques and choice of application. Materials in use for cardiopulmonary bypass have changed
and coated components have been used frequently. Improvements in the area of instrumentation were achieved
by adaptation of conventional cardiopulmonary bypass circuits. Miniaturization and re-design of cardiopulmonary bypass circuits (so-called minimized perfusion circuits or minimal extracorporeal circulation circuits)
have made cardiopulmonary bypass technology less traumatic. A team approach, including the cardiac surgeon,
the anesthesiologist and the cardiovascular perfusionist, was deemed beneficial in order to achieve further
improvements. Next to choice of technology and material for a given operation, adjunct measures such as
pharmaceutical treatment and blood conservation strategies need to be taken into consideration. Monitoring of
variables during cardiopulmonary bypass has made some progress, while the knowledge base has expanded due
to studies on best practices. For the immediate future, sound scientific knowledge and intelligent monitoring
tools will allow cardiopulmonary bypass to be tailored to individual patients’ needs.
Keywords: cardiopulmonary bypass, extracorporeal circulation, biocompatibility, minimized perfusion circuit, systemic inflammatory response.
Presented at the 3rd Expert Forum of the Roland Hetzer International Cardiothoracic and Vascular Surgery Society on the
occasion of the 6th Oriental Congress of Cardiology, Shanghai, May 25, 2012
INTRODUCTION
The development of cardiopulmonary bypass (CPB) has been an ongoing process
since its first clinical use. Equipment and
techniques have undergone significant refinements (1).
Frank Merkle
Academy for Perfusion
Today, this technology is used in more
than one million cases annually worldwide (2).
The optimal technical characteristics of a
CPB system for any given patient as well
as the optimal operative strategy are still
under debate. Recently, an array of articles
on best practices and guidelines for the conduct of CPB has been published.
Biocompatibility
According to a widely used definition, the
term biocompatibility refers to “... the abil-
211
F. Merkle, et al.
212
ity of a material to perform with an appropriate host response in a specific application” (3).
The extent of body reactions to the exposure
to non-physiologic materials is a function
of the characteristics of foreign materials
and the nature, location and length of time
in use (4). However, questions in conjunction with biomaterials are whether it is possible to synthesize biomaterial with reliable
predictability of its properties (appropriate
host response), and whether this material
has any effect on increased patient safety
during CPB (5). A more complex definition
of the term reads as follows: “Biocompatibility refers to the ability of a biomaterial
to perform its desired function with respect
to a medical therapy, without eliciting any
undesirable local or systemic effects in the
recipient or beneficiary of that therapy, but
generating the most appropriate beneficial
cellular or tissue response in that specific
situation, and optimising the clinically relevant performance of that therapy” (6).
Physiologically, several mechanisms prevent the organism from blood loss due to
injured blood vessels: the coagulation system, endothelium and regulatory proteins,
platelets and fibrinolysis. This hemostatic
system of a patient is activated during cardiac surgery with and without CPB (7).
Furthermore, the so-called systemic inflammatory response syndrome (SIRS) is triggered. Surgical trauma, blood contact with
CPB surfaces, endotoxemia and ischemia
trigger mediators, transcription factors and
adhesion molecules, leading to leukocyte
extravasation, lipid peroxidation, edema
and eventually cell death (8). Clinically,
SIRS can lead to coagulopathy, arrhythmias, endothelial dysfunction, neurological
manifestations and end organ failure (1).
In order to improve the above scenario, several strategies have been developed. First
of all, use of the heart-lung machine could
be avoided, whenever feasible. However,
activation of the hemostatic system is still
detectable in off-pump cardiac surgery (9).
A second strategy would be to use more
advanced perfusion circuits, such as minimized perfusion circuits (MPCs), for those
operations where conventional circuits are
not necessary. The biomarker profile measured during the use of MPCs is comparable
to the profile measured when conventional
circuits are in use (10).
Minimized perfusion circuits
Minimized perfusion circuits are usually
comprised of venous and arterial tubings, a
centrifugal pump, a membrane oxygenator
(optionally with integrated arterial line filter) and cannulae. A venous reservoir and
suction devices (vent and field suction)
are usually not incorporated (1). All components of the circuits are either heparin
coated or treated with alternative coating
agents.
The use of centrifugal arterial pumps is advocated. Further, low priming volume of
MPCs in contrast to conventional circuits,
the use of cell salvage devices instead of intraoperative retransfusion of untreated suction blood as well as venous line air handling devices are characteristics of these
miniaturized systems (11).
Initial concerns about a lack of safety in airhandling or cases of major blood loss could
be refuted by the results of studies focusing
on that matter. Kutschka et al. even demonstrated superiority in the handling of air in
an MPC compared to conventional bypass.
Modular concepts of MPCs allow the quick
integration of additional suckers and reservoirs if major bleeding occurs (12).
A variety of studies was undertaken in
order to determine differences in patient
outcomes when conventional CPB circuits
were compared to minimized perfusion
circuits. These early studies, however, included small patient groups with low risk
profiles. Subsequently, only limited evi-
State of the art in cardiovascular perfusion
Table 1 - Clinical experience and findings with MPCs.
Publication
Year
n
213
Groups
Procedure
CPB
MPC
Significant
differences
Remadi et al.
2006
400
elective CABG
200
200 (MECC)
a), b), c), d), e)
Abdel Rahman et al.
2005
204
CABG
103
101 (CorX)
a), c), d), f)
Huybregts et al.
2007
49
elective CABG
24
25 (Syn. ECC.O)
a), c)
Fromes et al.
2002
60
CABG
30
30 (MECC)
a), e)
Beghi et al.
2006
60
elective CABG
30
30 (MECC)
a)
Schöttler et al.
2008
60
CABG
30
30 (MECC)
a), d)
Remadi et al.
2004
100
AVR
50
50 (MECC)
a), b), c)
Castiglioni et al.
2009
120
AVR
60
60 (MECC)
a), d)
Bical et al.
2006
40
AVR
20
20 (MECC)
a), e)
Kutschka et al.
2009
170
AVR and CABG
85
85 (ROCSafe)
a), f)
El-Essawi et al.
2011
500
CABG and/or AVR
248
252 (ROCSafe)
a), b), d), e), f)
a) Blood transfusion, Hemodilution b) Neurological outcome, c) Renal impairment, d) Myocardial ischemia, e) Inflammatory
parameters, f) Length of stay in intensive care unit, respirator time
CABG = coronary artery bypass grafting; AVR = Aortic Valve Replacement; MECC = minimal extracorporeal circulation circuits
CPB = cardiopulmonary bypass; MPC = minimized perfusion circuits
Syn. ECC.O, Sorin, Mirandola, Italy; ROCSafe, Terumo, Eschborn, Germany; MECC, Maquet, Rastatt, Germany.
dence was available in favour of these circuits (13-16).
To date, a number of studies with prospective randomized design and a cohort of
more than 40 patients have been published
(17-22) (Table 1).
Vohra et al. describe the effect of minimized
circuits on inflammatory markers and endorgan effects.
Although a reduction in the amount of circulating inflammatory markers can be measured, the authors state that survival rates
of patients operated upon with conventional CPB do not differ from those of patients
operated on with MPC (1).
In contrast, Anastasiadis et al. in their
metaanalysis found that so-called minimal
extracorporeal circulation improved shortterm patient outcome by reducing the mortality and morbidity associated with conventional systems (23).
The requirement for blood transfusion is
today regarded as a risk factor for adverse
long-term outcome in cardiac surgery (24).
Avoiding transfusion by reducing hemodilution, caused by excessive priming volume
of conventional CPB circuits, is recommended. The use of mini-circuits is advocated especially in patients with high risks
for adverse effects of hemodilution (25).
MPCs are associated with significantly reduced hemodilution and higher hematocrit
at the end of the extracorporeal circulation,
as compared with conventional CPB (23).
A retrospective study on transfusion requirements in 285 coronary artery bypass
grafting (CABG) patients compared offpump procedures, conventional circuits
(with cold hydroxyethyl starch cardioplegia) and MPCs (with warm blood cardioplegia).
The authors stated that significantly fewer
F. Merkle, et al.
214
blood transfusions were needed in the MPC
group than in the off-pump and conventional CPB groups. For the conventional CPB
group, the use of thrombocyte concentrates
was higher on the day of operation than in
the MPC group. However, the results of this
study may be questionable, since the type of
cardioplegia differed between the on-pump
groups (26).
A metaanalysis of randomized controlled
studies, which included pooled data from
1051 patients, found that MPCs decreased
the risk of red blood cell transfusion and
the amount of red blood cells transfused
per patient when compared with conventional CPB in CABG patients (27).
In a prospective randomized multicenter
study (6 hospitals), an MPC device was
compared to conventional CPB. Five hundred patients were included; 252 patients
were assigned to the same type of MPC, 248
patients were assigned to the standard open
CPB system of the respective hospital.
In this study, favorable results were noted
for the MPC procedures regarding transfusion requirements, incidence of atrial fibrillation and the incidence of major adverse
events (death, myocardial infarction, major
cerebrovascular accidents, re-operation).
Furthermore, an optimal outcome, defined
as freedom from blood transfusion or any
adverse event, was clearly in favour of the
MPC group (52% vs. 41%; p = 0.02). The
findings are summarized in Table 2.
This study also showed significant differ-
ences regarding biochemical parameters in
favour of the MPC group. Beside platelets,
red and white blood cells, granulocytes and
lymphocytes, plasma free hemoglobin, creatinine and LDH were measured (22).
Miniaturized CPB in pediatric surgery
In analogy to the developments in adult cardiac surgery, interest in reducing hemodilution and the subsequent necessity for transfusion of homologous blood components
in pediatric cardiac surgery has increased
recently. Alongside the potential for transmission of infection, the use of fresh whole
blood for priming heart lung machines for
children and the use of blood components
are triggers for altered immunologic function. For this reason, avoiding blood components for priming of the CPB circuit may
have beneficial effects (28).
Miniaturization of conventional CPB has
been achieved in experimental surgery and
in clinical practice. The asanguineous priming fluid in the animal model described by
Hickey et al. was found to improve postoperative right ventricular function, pulmonary compliance, alveolar gas exchange,
recovery of cerebral perfusion and the inflammatory cytokine load (28).
Clinically, the use of an asanguineous prime
is feasible as well. Initial experiences with
blood-free priming of a conventional CPB
circuit for a neonatal cardiac operation (29)
showed that this approach was possible.
Subsequently, neonates in several series
Table 2 - Benefits of MPCs.
Variable
MPC
Conventional CPB
p-value
Total blood transfusion
333±603 ml
587±1010 ml
<0.001
PRBC
199±367 ml
347±594 ml
<0.001
FFP
Major adverse events
Myocardial infarction
124 ± 308 ml
9.1%
1.6%
268 ± 732 ml
16.5%
5.2%
0.01
0.02
0.03
PRBC = packed red blood cells; FFP = fresh frozen plasma; MPC = minimized perfusion circuit; CPB = cardiopulmonary bypass.
State of the art in cardiovascular perfusion
were operated on without the use of blood
prime (30, 31). In a retrospective analysis
on 288 children from the same institution,
children weighing from 1.7 to 15.9 kg were
divided into the three categories no transfusion, postoperative transfusion only,
and intraoperative as well as postoperative
transfusion.
Of these children, 24.7% did not require
any form of blood transfusion during their
hospital stay, 23.6% received transfusions
postoperatively, and 51.7% received intraand postoperative transfusion. It was noted
that this achievement was only possible
because of the concerted efforts of the surgeon, anaesthesiologist and perfusionist in
addition to the availability of the appropriate equipment (32).
evidence-based guidelines are of uncertain
reliability (35).
The term “goal-directed perfusion management” was created by the working group
of Ranucci et al. One of the key findings of
a recent publication is the statement that
oxygen delivery should be preserved by reducing hemodilution and maintaining high
pump flows, since a nadir oxygen delivery
of 262ml/min/m² during CPB is associated
with acute kidney failure (36).
In the future, more patient-targeted pharmaceutical strategies, including genetic
risk profiles for hemostatic activation, will
make it possible to select the appropriate
CPB technology for a given patient (7).
CONCLUSION
Conduct and monitoring of CPB
While the conduct of CPB was referred to
as “experience based” in contrast to based
on evidence only a short while ago (33), a
number of publications have subsequently
dealt with this issue.
Shann et al. gathered available evidence on
the practice of CPB in adults, mainly focusing on neurologic injury, glycemic control, hemodilution and the inflammatory
response. One of the recommendations of
this paper was to avoid direct retransfusion
of unprocessed blood exposed to pericardial
and mediastinal surfaces. Also, hemodilution should be minimized to avoid subsequent allogeneic blood transfusion (34).
In a following paper, Murphy et al. focused
on management of physiologic parameters
during CPB, namely on determinants of
tissue oxygen supply and demand, such
as mean arterial pressure, systemic bypass
flow rates, hematocrit values, oxygen delivery, systemic temperatures, pulsatility
and acid-base management. The authors
addressed these topics extensively, but also
concluded that since there is limited high
quality data on perfusion-related issues,
The combined strategies of avoiding excessive hemodiluion, decreasing CPB circuit
size, avoiding blood transfusion, limiting
the use of cardiotomy suction, and the use
of re-engineered and optimized perfusion
circuits may make cardiopulmonary bypass
more patient-friendly.
The knowledge base for cardiopulmonary
bypass related technologies has expanded,
and evidence-based guidelines have been
established in some areas. Well-controlled
studies on the effect of interventions are
warranted to help in choosing the right
technology for the right patient.
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Cite this article as: Merkle F, Haupt B, El-Essawi A, Hetzer R. State of the art in cardiovascular perfusion: now and in the
next decade. HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4 (4): 211-216
Acknowledgements: We thank Anne Gale, ELS (Editor in the Life Sciences), for editorial assistance.
gifZ\\[è^j
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EXPERT OPINION
!"#$%&"'()
Coronary artery surgery:
now and in the next decade
J.C. Ennker1,2, I.C. Ennker3
1
MediClin Heart Institute Lahr/Baden, Lahr, Germany; 2Institute of Cardiovascular Medicine, University Witten-Herdecke,
Witten, Germany; 3Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany
ABSTRACT
In coronary artery surgery the superiority of the internal mammary artery graft in 10-year survival was
documented in 1986. In 1999 it was demonstrated that death, reoperation and percutaneous transluminary
coronary angioplasty were more frequent in patients undergoing single rather than bilateral internal mammary artery grafting. Today coronary artery bypass grafting surgery is challenged by the success story of
modern interventional cardiology. The Syntax Study, however, clearly underlined the better outcome for
patients with triple-vessel and/or left main disease undergoing coronary artery bypass grafting in terms
of repeat revascularization. Another point of ongoing discussion is the comparison between on-pump and
off-pump coronary artery revascularization techniques. Even if mixed results exists in the literature, in
experienced hands the combination of aortic no-touch and total arterial revascularization, probably leads to
the superiority in off pump coronary artery bypass grafting in terms of significantly decreased rates of mortality, stroke, major adverse cardiac and cerebral vascular events. Coronary artery surgery in the next decade
will be influenced by the further progression of minimally invasive surgical principles and by a variety of
other factors. The role of robotics and hybrid surgery has yet to be defined. Alternatives within surgery will
not only need to move to a less disruptive strategy (e.g. from on-pump to off-pump bypass) but also have to
secure sustained innovation, as we can be sure that the current coronary artery bypass grafting activity will
change substantially.
Keywords: coronary artery revascularization, future aspects.
NOW Arterial revascularization Coronary artery surgery has been the cornerstone of treatment of coronary artery
disease since the introduction of aortocoronary bypass as a routine clinical procedure
by Favaloro in Cleveland in 1968 (1).
Prof. Dr. med. Jürgen Ennker
Medical Director
Department of Cardiothoracic and Vascular Surgery
MediClin Heart Institute Lahr/Baden
Lahr, Germany
In 1986 Loop and colleagues documented
the superiority of the internal mammary
artery graft for 10-year survival and other
cardiac events.
They had compared 2306 patients who received an internal mammary artery graft
to the anterior descending coronary artery
alone or combined with one or more saphenous vein grafts, with 3625 patients who
had only saphenous vein grafts.
They found that patients who had only
vein grafts had a 1.61 times greater risk of
death over a 10-year period, as compared
with those who received an internal mam-
217
J.C. Ennker, et al.
218
mary artery graft. Other disadvantages for
the isolated vein grafting were an increased
risk of late myocardial infarction (1.41 times), risk of hospitalisation (1.25 times),
risk of cardiac reoperation (2.0 times) and
risk of late cardiac events (1.27 times). This
technique is nowadays a routine in modern
coronary artery bypass grafting (2).
In 1999 Lytle, again from the Cleveland
Clinic, published a retrospective, non-randomized study with a mean follow-up interval of 10 postoperative years including
patients who received either single (8123
patients) or bilateral internal thoracic artery (ITA) grafts (2001 patients) with or
without additional vein grafts. Death, reoperation and percutaneous transluminal
coronary angioplasty were more frequent
in patients undergoing single rather than
bilateral ITA grafting. The differences were
greatest in regard to reoperation (decrease
of risk of reoperation by 12 years at least
8.3%) (3) (Figure 1). Although this finding
sent a clear message throughout the world
of coronary artery surgeons, this technique
has yet not found predominant use.
Coronary artery surgery - Syntax study
Today, coronary artery bypass surgery is
challenged by the success story of modern
interventional cardiology. The discussion
of which patient goes to what treatment
modality has been clarified by the recent
Syntax study. The Syntax study compares
outcomes of coronary artery bypass grafting with percutaneous coronary intervention in patients with triple vessel and/or
left main disease. Complexity of coronary
artery disease was quantified by the Syntax score, which combines the anatomic
characteristics of each significant lesion.
The study aimed to clarify whether Syntax
score affects the results of bypass grafting.
Outcome was defined by major adverse cerebrovascular and cardiac events and its
consequences over a period that is now
over 4 years (4) (Table 1).
The surgical advantages were relevant in
terms of repeat revascularisation, but also
underlined a significant surgical benefit concerning myocardial infarction and
survival rates. In patients associated with
greater complexity of coronary pathology,
Figure 1 - Superiority of bilateral internal
thoracic artery grafting.
CABG=coronary artery
bypass, BITA=bilateral
internal thoracic artery;
SITA=single internal thoracic artery.
Coronary artery surgery
Table 1 - Syntax Results after 4 years (Serruys P., EACTS Meeting 2011 Lisbon).
219
Cardiac
Revasc.
PCI/Stent
p-value
MACCE
(death, stroke, myocardial infarction, revascularisation)
23,6%
33,5%
<0,001
Death/Stroke/Myocardial infarction
14,6%
18,0%
0,07
Total mortality
8,8%
11,7%
0,048
Cardiac mortality
4,3%
7,6%
0,004
Stroke
3,7%
2,3%
0,06
Myocardial infarction
3,8%
8,3%
<0,001
Stroke
3,7%
2,3%
0,06
Endpoint MACCE = major adverse cerebrovascular and cardiac events; PCI/Stent = percutaneous coronary intervention
percutaneous coronary intervention demonstrated substantial disadvantages (5).
The Syntax study also recommended that
incomplete revascularisation is associated
with adverse events during follow-up after
percutaneous coronary intervention but
not following coronary artery bypass grafting. Another message of the Syntax study
is the recommendation of a heart team in
which the interventional cardiology and
the surgeon work closely together to provide adequate therapy for coronary artery
patients. The Syntax study should have a
substantial impact on the treatment of coronary artery disease. Its consequences are
already found in the new European Society
for Cardiology/European Association for
Cardiothoracic Surgery guidelines for myocardial revascularization (6).
On-pump vs off-pump
Another point of ongoing discussion is
whether on-pump or off-pump coronary
artery revascularization is superior for the
coronary artery disease patient. A recent
study that analyzed 4752 patients from
79 centers in 19 countries randomly assigned patients in whom coronary artery
bypass (CABG) was planned, to undergo
off-pump or on-pump CABG. The first coprimary outcome was a composite of death,
non-fatal stroke and non-fatal myocardial
infarction. The results demonstrated that
there was no significant difference between the two procedures with respect to the
30-day rate of death, myocardial infarction,
stroke or renal failure requiring dialysis.
The use of off-pump CABG, however, led
to reduced rates of transfusion, reoperation
for perioperative bleeding, respiratory complications and acute kidney injury, but also
revealed an increased risk of early revascularization (7).
Others reported that the quality of the
off-pump surgery, including the combination of aortic no-touch and total arterial
revascularization with complete revascularization, leads to the fact that off-pump
coronary artery bypass (OPCAB) patients
benefit from significantly decreased rates
of mortality, stroke, major adverse cardiac
and cerebral vascular events (MACCE). In
particular, the no-touch technique leads
to a significantly lower rate of stroke and
should therefore be the procedure of choice
in patients with atherosclerotic ascending
aortic disease (8).
These findings were underlined by a recent multicenter, randomized, parallel trial
which had enrolled patients for elective or
urgent isolated coronary artery bypass grafting with an additive European System for
J.C. Ennker, et al.
220
Cardiac Operative Risk Evaluation of 6 or
more. The composite primary end-point included operative mortality, myocardial infarction, stroke, renal failure, reoperation
for bleeding and adult respiratory distress
syndrome within 30 days after surgery.
A total of 195 patients could be treated onpump and 216 off-pump. According to the
intention to treat analysis, the rate of the
composite primary end-point was significantly lower (unadjusted P=.009, adjusted
P=.010) in the off-pump group (5.8% vs
13.3 %). The risk of experiencing the primary end-point was significantly greater for
the on-pump group. The authors concluded
that off-pump coronary artery bypass grafting reduces early mortality and morbidity
in high-risk patients (9).
Neurological complications
One of the most devastating complications
of coronary artery surgery is definitely a postoperative adverse neurological outcome,
as stroke or cognitive decline. Recent large,
prospective, randomized studies analyzing
the rate of negative neurologic outcome
after conventional on-pump surgery and
after off-pump surgery were not able to
show a significant risk reduction following
off-pump surgery, as it had been presumed.
As a consequence, investigations aiming to
reduce the incidence of adverse neurological outcome following bypass surgery have
shed light on the role of patient-related factors, such as the degree of atherosclerosis
of the aorta or pre-existing cerebrovascular
and systemic vascular disease and adequate preoperative screening and preparation,
instead of focusing on the impact of surgery-related factors.
In a paper addressing the cognitive and
neurological outcome after coronary artery
bypass surgery the authors concluded that
the risk for both points should not be influencing the choice of surgical therapy for
coronary artery bypass grafting. Rather,
strategies should focus on the preoperative
assessment of specific risk factors and on
an individualized surgical approach, especially in high-risk patients.
Undiagnosed cognitive impairment is not
rare in coronary artery disease patients
and is evaluated as a surrogate marker for
underlying cerebrovascular disease. Its
long time effect should be addressed predominantly by reducing modifiable risk
factors for cerebrovascular disease, since it
is well known that late cognitive decline is
more related to the progression of systemic
vascular disease rather than being a late
consequence of extracorporeal circulation
(10). Our own experience
In experienced groups with over 95% offpump procedures a mortality rate below
1% in elective patients can be achieved.
Our own therapy regimen is given in Table 2. By strictly adhering to the principle
of the aortic no-touch technique, we were
able to eliminate neurological deficits due
to embolism from the aorta directly related
to the surgical procedure and could document a 30 day mortality for our group of
0.6% in 2011.
Contributing was the principle of complete
arterial revascularization, whenever possible. Some surgeons at our institution could
reach, or are already close to, zero mortality. We also employed successfully the
principle of OPCAB in reoperative coronary artery surgery, which could be used in
the majority of our redo patients, excluding
those who had strong adhesions from prior
pericarditis.
Hybrid procedures
Hybrid coronary revascularization is combining minimally invasive coronary artery
surgery and percutaneous coronary intervention, thus allowing sternal preservation for the treatment of patients with
Table 2 - Current decision making in our institution in coronary artery surgery.
221
Decision making factors
Applied technique
Short description
Procedure of first choice
Clamp-less OPCAB with double
IMAs as T-graft or in situ configuration
OPCAB & No-touchtechnique & TAR
Octogenarians, insulin dependent
diabetes, severe COPD, short RIMA
Clamp-less OPCAB with LIMA and
radial artery/vein as T-graft
OPCAB & No-touchtechnique
Short or small RIMA
Tangential clamping of the aorta for
proximal vein anastomoses
OPCAB
4.
Conversions due to hemodynamic
instability, ischemia, intraseptal LAD
On-pump CABG, Single Clamp
OPCAB conversion
5.
Instable hemodynamics,
EF <25
On-pump CABG with LIMA & vein
graft or TAR
CABG (poss.: TAR)
1.
2.
3.
OPCAB = Off-pump coronary artery bypass; IMA = internal mammary artery; COPD = chronic obstructive pulmonary disease;
RIMA = right internal mammary artery; LIMA = left internal mammary artery; LAD = left anterior descending; CABG =
coronary artery bypass; TAR = total arterial revascularization; EF= ejection fraction.
multi-vessel coronary artery disease. Revascularization of the left anterior descending coronary artery can be achieved by a
robotically assisted endoscopic approach
or conventional minimally invasive direct
coronary artery bypass (MIDCAB) surgery. Early experience demonstrates the
safety of the procedure, with perioperative clinical results comparable to those of
conventional coronary artery revascularization.
Bonatti demonstrated the feasibility of a
quadruple coronary artery bypass using a
totally endoscopic technique (11).
Gender disparity
Female gender is still a risk factor for early
mortality following coronary artery surgery. A recent study by Lehmkuhl analyzed
1559 consecutive patients treated between
2005 and 2008. As a result, self-assessed
physical functioning should be more seriously considered in preoperative risk assessment, particularly in women.
Key mediators of the overmortality of women after CABG were age, physical function and postoperative complications
(12).
Current trend
Coronary artery surgery has been a subject
to constant change. To characterize trends
in patients’ characteristics and outcomes
after CABG over the past decade ElBardissi
et al. assessed 1,497,254 patients who had
had a CABG procedure at STS participating
institutions.
They concluded that from 2000 to 2009 the
risk profile of patients undergoing CABG
had changed, with fewer smokers, more
patients with diabetes and better medical
therapy characterizing patients referred for
surgical coronary revascularization. The
left internal artery had been nearly universally used and outcomes had improved
substantially, combined with a significant
decline in postoperative mortality and morbidity (13).
IN THE NEXT DECADE
Surgical perspective Coronary artery surgery in the next decade will be influenced by the further progression of minimally invasive surgical
principles. The role of robotics has yet to
J.C. Ennker, et al.
222
be defined. In hybrid coronary artery revascularization, the advantage of closed chest
revascularization has to be weighed against
the risk of repeat revascularizations due to
percutaneous coronary intervention in the
right and circumflex artery.
Time will show how the evolution of the
surgical techniques of CABG will develop.
One of the challenges of the future will be to
bring this progress in surgical technology to
broad-scale application at a time when third
world countries are lacking coronary artery
surgery altogether or to a large degree. New
treatment modalities for coronary artery
disease will affect the incidence of surgical
procedures as well as the decreased incidence of reoperations in patients in whom
modern surgical principles, as complete arterial revascularization, have been used.
Possible influence of drug therapy
In this regard it remains to be seen what
the consequences of modern drug therapy
concerning coronary artery surgery will be:
so far it is of relevance to know that, for
example, statins clearly improve the outcomes of CABG patients.
All patients undergoing CABG are candidates for life-long statin therapy and its initiation is recommended as soon as coronary
disease is documented (in the absence of
contraindications).
Statins should be restarted early after surgery. However, the optimal postoperative
lipid-lowering regimen remains unknown
and is still the subject of upcoming trials.
Therefore, statin prescription rates and patient adherence are examples of priorities
for future research (14).
Drivers of change
In addition to these, coronary artery surgery will be influenced substantially by a
variety of factors. Drivers of change will
be: the industry, the patient, the health service, the health service purchaser, the craft
of coronary surgery itself, the resident, the
surgeon, the media and the cardiologist, as
pointed out by Sergeant in 2004 (15).
Christensen and Raynor underlined that
we have to keep in mind that disruptive
strategies create a 37% chance of survival
versus only 6% for incremental strategies
(16). So alternatives within surgery will not
only need to move to a disruptive strategy
(e.g. from on-pump to off-pump bypass) but
also have to secure sustained innovation,
since we can be sure that the current CABG
activity will change substantially in the coming years. New strategies, numbers, facts
and figures are undoubtedly important but
what matters most, not only in coronary artery surgery in the next decade, will be the
basic existence of so-called soft factors as
morality, intelligence, excellence, integrity,
compassion and surgical judgment.
Definitely, coronary artery surgery will
have its own role during the next decade
and further into the future.
REFERENCES
1. Favaloro RG. Saphenous vein autograft replacement of severe segmental coronary artery occlusion: operative technique. Ann Thorac Surg. 1968; 5: 334-9.
2. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the
internal-mammary-artery graft on 10-year survival and
other cardiac events. N Engl J Med 1986; 314: 1-6.
3. Lytle BW, Loop FD. Superiority of bilateral internal thoracic artery grafting, it’s been a long time comin’. Circulation
2001; 104: 2152-4.
4. Mohr FW, Rastan AJ, Serruys PW, et al. Complex coronary
anatomy in coronary artery bypass graft surgery: Impact
of complex coronary anatomy in modern bypass surgery?
Lessons learned from the SYNTAX trial after two years. J
Thorac Cardiovasc Surg 2011; 141: 130-40.
5. Kappetein AP, Feldman TE, Mack MJ, et al. Comparison
of coronary bypass surgery with drug-eluting stenting fort
the treatment of left main and/or three-vessel disease:
3-year follow-up of the SYNTAX trial. Eur Heart J 2011;
32: 2125-34.
6. Taggart DP. Lessons learned from the SYNTAX trial for
multivessel and left main stern coronary artery disease.
Curr Opin Cardiol 2011; 26: 502-7.
7. Lamy A, Devereaux PJ, Prabhakaran D, et al. Off-pump
or on-pump coronary-artery bypass grafting at 30 days. N
Engl J Med. 2012; 366: 1489-97.
8. Polomsky M, Puskas JD. Off-pump coronary artery bypass
grafting – the current state. Circulation J 2012; 76: 784-90.
9. Lemma GM, Coscioni E, Centofanti P, et al. On-pump versus off-pump coronary artery bypass surgery in high-risk
patients: operative results of a prospective randomized
trial (on-off study). J Thorac Cardiovasc Surg. 2012; 143:
625-31.
10. Selnes OA, Gottesmann RF, Grega MA, et al. Cognitive and
neurologic outcomes after coronary-artery bypass surgery.
N Engl J Med 2012; 366: 250-7.
11. Bonatti J, Wehman B, de Biasi AR, et al. Totally endoscopic
quadruple coronary artery bypass grafting is feasible using
robotic technology. Ann Thorac Surg 2012; 93: 111-2.
12. Lehmkuhl E, Kendel F, Gelbrich G, et al. Gender-specific
predictors of early mortality after coronary artery bypass
graft surgery. Clin Res Cardiol. 2012; 101: 745-51.
13. ElBardissi AW, Aranki SF, Sheng S, et al. Trends in isolated
coronary artery bypass grafting: an analysis of the society
of thoracic surgeons adult cardiac surgery database. J Thorac Cardiovasc Surg 2012; 143: 273-81.
14. Kulik A, Rule M. Lipid-lowering therapy and coronary artery bypass graft surgery: what are the benefits? Curr Opin
Cardiol 2011; 26: 508-17.
15. Sergeant P. The future of coronary bypass surgery. Eur J
Cardiothorac Surg 2004; Suppl. 1: 4-7.
16. Christensen CM, Raynor ME. The innovator’s solution Creating and sustaining successful growth. Harvard Business School Press (ISBN 1-57851-852-0); 2003.
Cite this article as: Ennker JC, Ennker IC. Coronary artery surgery: now and in the next decade. HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4 (4): 217-223
223
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EXPERT OPINION
!"#$%&"'()
Clinical results of implanted tissue
engineered heart valves
P.M. Dohmen
Department of Cardiac Surgery, Heart Center Leipzig, University of Leipzig, Leipzig, Germany
ABSTRACT
Since the first heterotopic implantation of a biological heart valve in 1955 by Murray, bioprostheses have been
steadily improved. For allografts different methods have been evaluated and modified to stabilize and preserve
the available tissue. Xenografts were fixed to cross-link the connective tissue as well as prevent immunogenic
reactions. Nevertheless, gluteraldehyde fixation leads to structural deterioration, which could only be partially
reduced by different kinds of anti-mineralization treatment. Due to preservation and fixation, allografts and
xenografts become non-viable bioprostheses with a lack of remodelling, regeneration and growth. Tissue engineering is a possible key to overcome these disadvantages as it will provide living tissue with remodelling,
regeneration and growth potential. This overview will look at the key points to provide such tissue engineered
heart valves by creating an appropriate scaffold where cells can grow, either in vitro or in vivo and remodel a
neo-scaffold which will lead to a functional autologous heart valve, and show initial clinical results.
Keywords: tissue engineering, clinical, remodelling potential.
occasion of the 6th Oriental Congress of Cardiology, Shanghai, May 25, 2012.
INTRODUCTION
Cardiovascular diseases are the most common reason for morbidity and mortality in
western countries.
Treatment of valve diseases is, beside coronary bypass surgery, the most common
therapy in cardiac surgery. Worldwide approximately 300,000 heart valve operations
are performed and since the introduction
of catheter-implantation techniques, transapical and transfemoral, the number has
further increased. In Germany each year
P.M. Dohmen, M.D Ph.D
Department of Cardiac Surgery,
Heart Center Leipzig, University of Leipzig,
Struempellstrasse 39, D-04289 Leipzig, Germany
around 20,000 heart valve procedures are
performed (1). If valve reconstruction cannot be performed, valve replacement will
be necessary. Today mechanical or biological heart valves are routinely used; however, both types of prosthesis show specific
limitations. Mechanical heart valves work
satisfactorily over many years after implantation but life-long anticoagulation needs to
be taken (2).
With biological heart valves full anticoagulation is not necessary and only low
doses of anti-thrombogenic therapy will
be sufficient but these valve prostheses are
limited due to tissue deterioration (3). Human tissue valves show ideal hemodynamic
performance; however their availability is
limited and due to immunogenic activity
225
P.M. Dohmen
226
these valves degenerate with time (4-9).
None of these heart valves show growth
potential, which implicates reoperations in
young patients (10). Therefore a new generation heart valve is needed to overcome
these disadvantages, showing the benefit of
a healthy viable tissue valve with remodelling, regeneration and growth potential.
Tissue engineering could be able to create
such a heart valve with all the advantages
of a regular healthy valve (11, 12).
This paper presents a review of the clinical use of different tissue engineered (TE)
heart valves, starting with a three-dimensional scaffold, which will be seeded in
vitro or in vivo with autologous cells (1317).
Concept of tissue engineered heart valve
Tissue engineering was defined by Nerem
(18) as the “development of biological substitutes to restore, maintain or improve
function”.
To create a viable heart valve by tissue engineering, a fundamental understanding
of the natural complexity of heart valves
is needed. Schoen et al. (19) showed the
evolution of the tissue architecture and cell
phenotypes in a heart valve through senescence. In the late fetal period, the main
components of the extracellular matrix are
glycosaminoglycans, whereas during the
next period the collagen and elastin start to
be organized and finally show a trilaminar
structure.
Furthermore the cell component density
will change with time, which means that
during the early phase of valve development there will be a decrease in the cell
components within the valves at adult age.
Additionally, valvular interstitial cell phenotype expression will also undergo an
evolution, as demonstrated by Aikawa et
al. (20), who showed differences in protein
expression. This knowledge is essential to
create a viable TE heart valve.
Scaffolds
Understanding the natural development of
a heart valve is essential to create an appropriate scaffold, based either on a polymer or
decellularized origin. In a previous review
article we described the importance of different aspects of a scaffold or matrix, which
should be fulfilled to allow natural behaviour. The following should be considered:
mechanical and biological integrity, providing dynamic and biochemical signals, allowing cell attachment and migration, securing diffusion of vital cell nutrients and
expression factor and allowing dynamic
changes of the scaffold architecture (21).
Two different possibilities are available to
create such a scaffold, namely polymers or
decellularized scaffolds.
Polymer scaffolds. The first synthetic polymer scaffolds were created with polyglycolic acid (PGA) and later additionally supported by polylactic acid (PLA) (22). The
advantages of synthetic scaffolds are the
unrestricted availability in each size at any
time and that sterility is not an issue. In vivo
experiments, however, have showed several disadvantages. One major issue was the
stability of the scaffold, which was already
problematic at low pressure circulation
(23). Therefore Sodian et al. (24) modified the PGA scaffold by using thermoplastic polyesters polyhydroxyalkanoates and
poly-4-hydroxybutyrate, which allowed
better handling to mould a trileaflet heartvalve shape. Hoerstrup et al. (25) combined
PLA with poly-4-hydroxybutyrate; however, this modification showed progression
of valve regurgitation and stenosis over
time. Furthermore DNA levels at 20 weeks
were higher than in native heart valve tissue which needs to be observed. This overshoot of valvular interstitial cell ingrowth
is probably due to the lack of biochemical
signals of the extracellular matrix (26).
Regeneration of biological valve is based on
proteolysis, whereas synthetic scaffolds are
Tissue engineered heart valves
degraded through hydrolysis. No answers
are yet available on the circulation of reciduals after the hydrolysis of the scaffold
is completed (27). At this time, however,
degradation will mainly take place in vitro
and therefore this risk should be limited.
Generally, these created TE heart valves are
simple tubes with leaflets, except for a synthetic scaffold newly developed by Sodian
et al. (28) which also offers sinuses. Recent
studies on aortic valve reconstruction focus
on the sinus function, which supports the
valvular function and improves durability
(29, 30). Today there are no clinical data
available on TE heart valves based on polymer scaffolds.
Decellularized scaffolds. Biological-based
scaffolds are an alternative to create a
three-dimensional scaffold. Therefore a
normally configurated heart valve, either
allo- or xenogenic nature, will be decellularized. Several decellularization techniques
are available, which are mostly a combination of different elements, namely nonionic and ionic detergents, chelating agents
and enzymatic methods (21). Up until now
four decellularization methods have been
clinically used, following two different concepts. The difference depends on the use
of in vitro reseeding in which a bioreactor
is needed. The second concept is based on
the implantation of a decellularized heart
valve which will be reseeded in vivo by the
patient’s body. In this case the patient is his
or her own bioreactor.
Booth et al. (31) compared different decellularization methods and found that only
deoxycholic acid (DOA) and sodium dodecyl sulfate (SDS) were able to completely
decellularize tissue. Furthermore there was
no destruction of the extracellular matrices
seen, which means there was preservation
of collagen, elastin and the glycosaminglycans. Rieder et al. (32) showed that SDS
might destabilize the triple helical domain
of collagen and lead to tissue deterioration.
Bodnar et al. (33) noted that the extracellular matrix swells by the use of SDS due to
destruction of extracellular proteaglycans
and glycosaminglycans. Additional studies
performed by Caamano et al. (34) showed
cytotoxicity of SDS which will have an influence on the ingrowth of host valvular
endothelial and interstitial cells. Kasimir
et al. (35) also showed highly variable efficiency of different decellularization treatments in which Triton-X100 and DOA
showed the best preservation of the extracellular structures.
Another important issue is the age of the
heart valve at the time of decellularization.
Stephens et al. (36) showed the different
habits of the matrix during maturation.
The extensibility differed significantly over
time, as a result of age-related shift of material properties of the heart valve with an
increase of collagen throughout the valve
layer, particularly at the fibrosa and ventricularis layers, as well as an increased
density of myofibroblasts.
These findings are in correlation with the
previously mentioned study by Schoen et
al. (19). Sterilization of decellularized matrices is another important issue, which has
been discussed in a previous paper (17).
Most of these tissue engineered heart valves
have been implanted so far in the low pressure system; however, limited experience is
available of implantation into the systemic
circulation (17).
Valvular cells
To construct a TE heart valve, autologous
valvular cells are needed to be seeded on the
three-dimensional scaffold. The cell types
needed for seeding are endothelial and interstitial valvular cells, which cannot be harvested, and therefore alternative cell populations are needed.
During the early days, vascular endothelial cells were harvested and multiplied in
vitro to be seeded later on a prepared ma-
227
P.M. Dohmen
228
trix. Dohmen et al. (37, 38) used venous
endothelial cells, for which an additional
intervention or operation is necessary.
The advantage of this strategy is the use of
end-differentiation cell types in which all
cell functions are preserved; however the
growth potential is limited. Endothelial cell
seeding prior to implantation creates an
anti-thrombotic surface and on the other
hand covers the collagen against possible
immunogenic reactions (39). Although the
presented results are excellent, there are
limitations as harvesting and cultivation
are delicate procedures. The risk of contamination by interstitial cells is always
present, which will overgrow endothelial
cells. If cell cultures are contaminated, another piece of vein needs to be harvested.
Sometimes endothelial growth in vitro is
limited due to the quality of autologous
serum. Therefore controlled pooled serum
is needed to overcome lack of endothelial
cell growth. Meinhart et al. (40) studied
the impact of serum lipid content, which
is crucial for endothelial cell proliferation.
Schaefermeier et al. (41) investigated the
complexity of endothelial cells. Depending
on the position of the endothelial cells, a
different marker will be expressed. Similar
results were found for interstitial specific
expression makers but remodelling processes of the extracellular matrix differed.
Therefore additional studies are needed to
evaluate the possibility of reprogramming
endothelial cells at other locations.
New cell sources with increased growth
potential need to be evaluated. Progenitor
cells could be a good alternative for creating endothelial cells, for example human
umbilical-cord-derived progenitor cells
(42). The disadvantage with these potential
cells will be the need to establish a cell bank
in which these cells need to be stored for
every individual patient. In addition, the
influence of long-term storage on growth
and multiplying capacity is still unknown.
Vincentelli et al. (43) showed that the use
of autologous bone marrow mononuclear
cells showed extensive tissue deterioration
and calcification after application to a decellularized valve scaffold in a juvenile sheep
model. Mesenchymal stem cells showed
excellent hemodynamic and histological
results but may enhance inflammatory and
thrombotic reactions. Rotmans et al. (44)
investigated the potential of bone-marrowderived endothelial progenitor cells, which
are a subset of anti-CD34 cells with excellent in-vitro proliferation and the potential
to differentiate into mature endothelial
cells. Their results with cell seeding, however, showed a strong increase of intimal
hyperplasia in the anti-CD34 seeded grafts
compared with the bare grafts.
Therefore additional studies are needed
to improve the reprogramming of valvular
progenitor or stem cells.
Clinical studies of tissue engineered
heart valves
The first clinical implantation of a tissue
engineered heart valve was performed in
2000, as published by Dohmen et al. (37),
showing the results of an in vitro seeded decellularized pulmonary allograft implanted
during a Ross operation in an adult patient. Further patients were treated with
these heart valves. Ten year clinical results
of these tissue engineered heart valves are
promising; however, only a limited number
of patients were included (14).
In another study decellularized xenogenic
pulmonary valves were seeded in vitro and
implanted. The mid-term results of these
tissue engineered heart valves are also
promising (38).
Cebotari et al. (45) published initial results
on tissue engineered heart valves in which
autologous progenitor cells were seeded
on an alternative decellularization treated
scaffold. The follow-up was 40 months,
showing respectable pressure gradients
and only mild to moderate regurgitation. In
vitro seeding of decellularized heart valves
is time consuming and demanding and alternatives have been introduced in clinical
application after extensive experimental
studies performed on the use of non in vitro
seeded tissue engineered heart valves. Da
Costa et al. (13) were able to show excellent hemodynamic behaviour of decellularized allografts compared with standard allografts. Furthermore they showed in this
study a statistically significant decrease
in HLA class I and II antigens in decellularized allografts compared with standard allografts: respectively 1.22±1.69
and 5.37±2.25 (p<0.01) and 1.04±1.59
and 5.92±1.66, respectively (p<0.001).
Konertz et al. (46) showed in a consecutive study the results of 50 adult patients
receiving a decellularized xenogenic heart
valve during the Ross procedure. With a
maximal follow up of 2 years, this study
showed encouraging data on the use of this
concept.
Brown et al. (16) found that the Synergraft
technology in allografts showed similar
freedom from reoperation rates in 342 patients with cryopreserved and synergraft
pulmonary valves who underwent Ross operation as well as right ventricular outflow
tract reconstruction. Pressure gradients at
the latest follow up were also similar in the
two groups; however, valve regurgitation
differed between the groups, in favour of
the cryopreserved valve using the Synergraft technology.
Nevertheless negative results have also
been found in clinical practice, as shown
by Simon et al. (47). They showed that the
Synergraft technology failed in 4 grafts after 2 days and 1 year post-implantation. Using decellularization techniques no recellularization of the decellularized grafts was
seen at up to 1 year of follow up. Rüffer
et al. (48) published an article about early
failure of decellularized pulmonary valves
in congenital cardiac surgery, which was
probably due to inflammatory response of
the extended pericardial patch which was
used and not neutralized. Interestingly, in
this study the failure was mainly seen in
the larger sizes than in the smaller sizes.
Oversizing of implanted heart valves is a
delicate issue in congenital cardiac surgery
and should be avoided as it can lead to early
graft failure. Cebotari et al. (49) were able
to show improvement of freedom from explantation of fresh decellularized allografts
compared with gluteraldehyde-fixed bovine jugular vein valves and cryopreserved
allografts of 100%, 86 ± 8% and 88 ±
7%, respectively, at 5 years of follow-up.
The mean pressure gradient of the fresh
decellularized allograft was significantly
lower than that of the gluteraldehyde-fixed
bovine jugular vein valves: 11 mm Hg versus 23 mm Hg, respectively (p=0.001). In
a recently published article Konertz et al.
(15) showed in infants freedom from reoperation or reintervention due to valve dysfunction of 94% at one year and 84% at 3
years in patients undergoing complex congenital cardiac surgery. Compared to other
available studies with regular heart valves
these results are promising.
Zehr et al. (50) showed favourable results
of decellularized cryopreserved aortic homografts in 22 patients using this graft
for root replacement. Low panel reactive
antibody response was seen, which may
enhance durability by reducing immunogenicity of these allografts.
Da Costa et al. (51) showed results for decellularized aortic homograft implants as a
root replacement in 41 patients. No reoperations were performed due to aortic valve
dysfunction with a maximal follow-up of
53 months. One patient, however, needed
reoperation on the mitral valve. After approval by the ethics board and patient,
a tiny biopsy of the aortic wall was performed showing that it was partially recel-
229
P.M. Dohmen
230
lularized at 18 months, without distortion
of the extracellular matrix.
In summary, first clinical implantations of
tissue engineered heart valves seeded either in vitro or in vivo have been performed.
Several studies have been conducted of reconstruction of the right ventricular outflow tract and now initial studies have been
initiated to implant these heart valves into
the systemic circulation.
15.
16.
17.
18.
19.
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Care and Cardiovascular Anesthesia 2012; 4 (4): 225-231
231
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EXPERT OPINION
!"#$%&"'()
Management of sterno-mediastinitis
I.C. Ennker1, J.C. Ennker2,3
1
Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany; 2MediClin Heart
Institute Lahr/Baden, Lahr, Germany; 3Institute of Cardiovascular Medicine, University Witten-Herdecke, Witten, Germany
ABSTRACT
With an incidence rate of 1-4%, mediastinitis following cardiac surgery is a rarely occurring complication,
but may show a mortality rate of up to 50%. Risk factors for sternal instability are insulin-dependent diabetes
mellitus, obesity, immunosuppressed state, chronic obstructive pulmonary disease, osteoporosis, history of radiation, renal failure, body height, smoking and nutritional state. The aim of this paper is to show an overview
of this clinical picture, present the risk factors and elucidate the therapy options chronologically. As a result
of interdisciplinary cooperation, a therapy concept has developed which is adapted to the patient individually. Therapy begins with the simplest measures and, if deemed necessary, this is then escalated step by step.
The aim of the treatment is to bring the infection under control, which requires radical surgical debridement,
removal of infected and necrotic tissue, removal of all foreign bodies (including wires and osteosynthesis material) and the removal of all infected, necrotic osseous material if necessary followed by vacuum-assisted closure
therapy. The reconstruction of defects of the anterior chest wall is achievable using different muscle flaps.
Mostly the muscle pectoralis major is used unilaterally or bilaterally with or without disinsertion of the tendon. Other options are the omental flap, the muscle latissimus dorsi flap or the muscle rectus abdominis flap. A
combined approach comprising surgical debridement, short-term vacuum therapy and subsequent myoplastic
coverage has proved successful and can be carried out with a high standard of safety.
Keywords: sternotomy, sternal infection, therapeutic options, interdisciplinary cooperation.
INTRODUCTION
In the treatment of mediastinitis and sternal osteomyelitis, a change of treatment
is emerging from open as well as vacuum
and irrigation procedures toward combined
procedures. The current gold standard is
early and radical surgical debridement, followed by vacuum therapy and plastic surgery reconstruction.
Priv.-Doz. Dr. med. Ina Carolin Ennker, FETCS
Department of Plastic, Hand and Reconstructive Surgery
Hannover Medical School
Carl-Neuberg-Straße 1
30625 Hannover, Germany
Sternal infections and mediastinitis can result from infections, tumors, injuries or as
a consequence of radiotherapy.
The commonest cause of sternal wound infections is sternotomy. Median sternotomy
is the standard access for cardiac surgery
interventions.
Despite the undisputed advantages of this
route of access, severe complications may
occur, which lead to further interventions
with an extended hospital stay and increased costs for the health system. Another consequence is a reduced long-term
survival rate (1-3). Complications are
principally divided into infection-induced
vs. non-infection-induced and stable vs.
233
234
instable conditions. The most severe complication for the patient is mediastinitis
with concomitant instability of the sternum.
An initially uncomplicated instability may
cause an infection with subsequent mediastinitis. Mediastinitis accompanied by initially stable sternum conditions inevitably
leads to instability sooner or later (4).
Incidence and risk factors
With an incidence of 1-4%, postoperative
mediastinitis and sternal osteomyelitis is
rare (3, 5, 6). However, the complications
arising as a result of perioperative infections show a significant mortality rate up
to 50% (3, 6), on average 10-25% (7).
Considered as risk factors for this postoperative complication are insulin-dependent
diabetes mellitus, obesity, immunosuppression, chronic obstructive pulmonary
disease (COPD), sternal osteoporosis, irradiation of the operated area, use of bilateral
internal thoracic arteries as bypass grafts,
decreased or increased body mass, renal
failure and inadequate surgical techniques
Thoracic wall tumors may also lead to infections with subsequent mediastinitis (4,
6, 8-12). The diagnosis of postoperative
mediastinitis or sternal osteomyelitis usually occurs in a clinical setting based on
the typical signs of a local wound infection. The majority of patients show wound
secretion accompanied by leukocytosis, an
elevated C-reactive protein (CRP) value as
well as elevated body temperature. Half of
the patients have sternal instability in addition.
On the basis of clinical study, crepitation
is apparent. Some patients, however, also
arrive for admission with an open wound
and in some cases with torn out and exposed sternal wires. In uncertain cases, a
computed tomography (CT) or magnetic
resonance tomography (MRT) may help in
the decision-making process.
Figure 1 - Deep sternal infection 6 weeks post
surgery.
Classification of mediastinitis
Mediastinitis (Figure 1) is defined in accordance with the guideline of the US Centers
for Disease Control and Prevention (CDC)
as an A3 infection. This means that the infection appears within 30 days or within
one year in the case of implants and fulfills
at least one of the following criteria:
- purulent secretion from the drainage tube
connected to the organ or body cavity;
- spontaneous opening of the wound,
reopening at temperatures over 38° or
pain as well as isolation of pathogens
from a culture taken under sterile conditions from the organ or body cavity;
- abscess or other sign of infection during
the course of reoperation, clinical examination, histopathological examination
or imaging procedures;
- diagnosis of the attending surgeon/physician (13).
Therapeutic options
There is currently no general consensus regarding appropriate postoperative surgical
therapy for mediastinitis (7). The goal is to
control the infection and to achieve prompt
sternal stability with adequate soft tissue
coverage (3, 11). Wound healing strategies
comprise open wound treatment, vacuum
and irrigation drainage, vacuum-assisted
closure therapy (VAC) and reconstruction
using flap plasties.
Chronologically, the first procedure was
open wound treatment. This includes reopening the sternum, surgical debridement,
changing dressings with moist compresses
up to spontaneous wound closure by granulation and epithelialization. Because of
their high failure rate and a mortality rate
of over 50% due to sepsis, tissue erosion or
direct injuries of the right ventricle caused
by the sternum or sharp-edged fragments,
these methods were dropped (4, 14).
Chronologically, this was then followed by
vacuum and irrigation drainage. This also
included reopening the sternum, surgical
debridement of the entire area as well as
removal of osteosynthetic material. This
is followed by extensive irrigation of the
wound and the insertion of a vacuum-irrigation system retrosternally. The sternum
is then closed in the conventional manner,
the soft tissues closing in layers (4, 5).
This is followed by continuous or intermittent irrigation, until three pathogen-free
effluates are obtained from the irrigation
fluid. If this does not succeed, the vacuumirrigation therapy should be terminated after four weeks at the latest. The advantages
of this technique are immediate sternal stability and soft tissue closure.
Disadvantages of the method are the creation of possible dead spaces (irrigation
channels), the risk of catheter erosion of
vital organs and the danger of systemic absorption of the vacuum-irrigation fluid or
a tamponade. And there is little influence
of infected soft tissue. Due to its high morbidity and mortality rate of up to 36%, this
method should now only be applied in exceptional cases.
Use of vacuum assisted closure therapy
A promising approach in the treatment of
mediastinitis following heart surgery is the
VAC -therapy, a secondary healing system.
This was introduced by Argenta and Morykwas in 1997 (15, 16) and is based on the
application of a uniform local vacuum of up
to 120 mmHg in the wound area.
Chronic and partly also acute and sub-acute
wounds are characterized by peripheral
edema, which impedes microcirculation
and lymph drainage. The uniform vacuum
acting on the wound causes removal of fluid
and a reduction of pressure in the local tissue. This leads to a dilatation of the capillaries and improves the flow properties of the
blood, arterial blood flow, proliferation of
granulation tissue and angiogenesis. Secretion and debris are continuously removed
and the bacterial count drops (17). Recent publications show promising results,
although the number of cases observed is
limited and the underlying healing mechanisms are relatively unknown (18). VAC
should be performed for a short a time as
possible and serves as an interim measure
until final soft tissue reconstruction. (19).
There are only a few contraindications described in the literature for the application
of VAC. Thus, some patients report on pain
if the system was installed near their chest
wound.
In others, excessive growth of granulation
tissue into the sponge occurred, above all
when sponges were not changed in a timely
fashion. Both disadvantages can be readily
brought under control, however, if the pressure is applied slowly and does not drop below 120 mmHg and the sponge is changed
regularly (15, 16, 20, 21).
Use of flaps
The reconstruction by flaps was introduced
by Jurkiewicz in the early 80’s.
The reconstruction of the anterior chest
wall may be achieved by local pedicled or
free flaps (Figure 2). For example:
1) musculus pectoralis major;
2) transposition of the greater omentum;
235
236
Figure 2 - Options for flap plasties of the anterior chest wall.
3) musculus latissimus dorsi;
4) musculus rectus abdominis.
These autologous tissues are ideally suited
for covering surfaces with well-vascularized tissue, filling possible dead spaces as
well as ensuring coverage of exposed parts
of the sternum (4, 9, 22-24).
In principle, surgical reconstruction can
be achieved by using autologous tissue or
synthetic material. Most chest wall defects
can be treated with local, musculocutaneous tissue, in infection-induced defects following sternotomy in particular using the
pectoralis major (11).
Pectoralis muscle
Having excellent rotational capability, the
pectoralis major offers the possibility of
covering at least the upper two thirds of
the sternum. The pectoralis major muscle
can be used uni- or bilaterally. It is preferably dissected off the sternal origin, mobilized up to the humeral insertion and, if
deemed necessary, detached there (4, 11,
14, 22, 25). Additional length is given by
dissection of the flap from the costal origins and the clavicular part. But one has
to keep in mind, that the pars clavicularis of the muscle stays untouched. Acting this way the pedicle can be completely
isolated on the thoraco-acrominal trunk.
With an intact ipsilateral internal thoracic
artery, it can also be detached from the humeral insertion to perform a turn over flap.
The dissection starts performing the tendon desinseration at the humerus, followed
by the costal parts, the blood supply of the
thoraco-acrominal trunk and is completed
by raising the muscle from the clavicular
part. The blood supply is guaranteed by the
secondarily determined perforators of the
internal thoracic artery. The pedicle can be
turned into the sternal defect. Optically, it
is not possible to avoid the formation of a
protrusion, which some patients find disturbing (4, 11). In the presence of an advanced infection, parasternal vascularization is unreliable or destroyed.
For extensive defects, especially on the
lower third of the sternum, pectoralis major
flaps can also be dissected with the rectus
muscle in continuity and be implemented as
a so-called bridging flap. When doing this,
Figure 3 - Therapeutic options to reconstruct
defects with the pectoralis major.
if possible, the ipsilateral internal thoracic
artery should be intact (11, 24) (Figure 3).
The distal section of the wound is at particular risk, as here the greatest force of gravity and most movement acts on the ribcage
and the pectoralis muscles are by their nature least developed (4).
Omentum flap
The greater omentum (Figure 4) is perfused
with blood by the gastro-epiploic vessels
along the greater curvature of the stomach.
It contains many immunologically active
cells and shows anti-infective activity (4,
11, 26, 27). The greater omentum has a
wide range; the mediastinum can be filled
in satisfactorily. The flap can be pedicled
Figure 4 - Greater omentum harvested.
Figure 5 - Transposition into the defect.
237
Figure 6 - 12 days post surgery.
via the right as well as via the left gastro-epiploic artery. Many surgeons prefer transpositioning of the greater omentum, above
all, if foreign material lies exposed and irrigation channels have to be filled.
Together with adequate surgical debridement, resolute intensive care as well as antibiotic monitoring, the method markedly
improved the clinical results and concomitantly reduced the length of time in the
prone position for the patient. It is, however, a two-cavity intervention with all the
complication possibilities associated with
this and a mortality rate of 12-36% (27)
(Figures 5 and 6).
Further problems, influencing the local
zone of defect coverage, are the protracted
secretion and possibly necessary skin transplants. Hernias also occur.
Latissimus dorsi muscle
This muscle receives its blood supply via
the thoracodorsal artery and intercostal
and lumbar perforators. The latissimus
dorsi flap can be implemented as a pedicled,
single or double flap as well as a free flap
plasty (11, 14, 28).
The anterior thoracic wall can usually be
readily reached by the pedicled muscle flap.
There is a wide and reliable radius of rotation. The skin islets can measure a good 10
238
cm and can be oriented horizontally, vertically and obliquely. Whilst preparing the
flap, the patient must be positioned onto
his side so that repositioning may be necessary during the operation.
The donor side morbidity following pectoralis muscle is low. Effects on respiratory
capacity are rare and are considered unproblematic. However, the effect on respiratory capacity is greater after using the rectus abdominis muscle as a reconstruction
measure.
The donor side morbidity following latissimus dorsi plasty is a little higher, and there
is the disadvantage of changing position
during operation.
Rectus abdominis muscle
Some authors favor the sole use of the rectus
abdominis muscle. For sternal reconstruction, they are suitable as cranially pedicled
flaps (11). Hernias occasionally occur as a
complication. This technique should only
be applied in ipsilaterally intact internal
thoracic arteries. Otherwise there is an increased danger of necrosis (see the paragraph
“Pectoralis muscle” and Figures 2 and 3).
Along with the increased logistic investment, the following disadvantages of the
muscle flap plasties also have to be considered (24):
- hematomas and seromas with subsequent revision;
- necrosis and wound healing disturbances;
- dysaesthesias in the operation area for a
considerable time after the intervention;
- abnormal sternal mobility under stress
such as cough or lateral position as a
consequence of an unhealed sternotomy;
- tension and excessive distension in the
distal scar area in female patients with
mammary hyperplasia (29).
Concerns regarding restricted pulmonary
function following reconstruction by means
of muscle flaps could be dispelled (11, 14,
22, 24, 25). Postoperative pulmonary function tests show no relevant difference in
comparison to the preoperative results.
Therapy algorithm
All aforementioned established procedures
partially show high morbidity and mortality rates. Therefore, it continues to be
important to develop alternative, safe therapeutic procedures. Common to all procedures, taking the central criteria (Table 1)
into consideration, is the goal of bringing
about healing of the sternal infection.
To achieve this, one should begin in the
form of a “therapy ladder” (Table 2) with
the simplest measure and then step-by-step
escalate the therapy. In our patient collective, we use multistep therapy with phasespecific procedures and the following algorithm:
- complete removal of the infected and necrotic tissue and all foreign material, bacterial monitoring and antibiotic therapy;
- restabilization of the sternum depending on the findings and the time interval
from the first operation;
Table 1 - Central treatment criteria.
-
Radical surgical debridement of all infected
and necrotic material, removal of all foreign
bodies (osteosynthetic material)
Bacteriological monitoring with antibiotic
therapy according to an antibiogram
Coverage of vital structures
Re-establishment of functionality
Stabilization of the bony skeleton
Filling of empty body (residual) cavities
Consideration of aesthetic aspects
Table 2 - Therapeutic ladder.
-
Conservative approach, secondary wound healing
Hydrotherapy, VAC therapy
Direct wound closure
Split skin flaps
Local/regional flap plasties
Free flap plasties
VAC = vacuum-assisted closure
- application of VAC;
- plastic surgery coverage after abatement
of the infection parameters with pectoralis muscle plasty.
Radical, extensive debridement encompassing all infected structures is indispensable,
also meaning that all osteosynthetic material has to be removed. A continuing infection can otherwise maintain progressive
necrosis and in this way destroy tissue that
is necessary for myoplastic coverage. The
same applies for infected or necrotic bony
parts of the sternum or the rib insertions.
Partial or complete sternectomy may be
necessary (11).
Non-infected, vital sternum parts should be
preserved to improve thoracic stability and
to avoid postoperative respiratory insufficiency. Subsequently, the entire wound
must be extensively mechanically cleaned
and irrigated. At each debridement swabs
are taken and therapy is completed by administration of an antibiotic according to
an antibiogram. With suitable wound conditions direct wound closure may be carried out. Otherwise VAC is recommended.
The sponge selected for this should be as
small as possible to avoid the soft tissues
from shrinking, thereby facilitating later
myoplastic reconstruction considerably.
Surgical debridement must be repeated until the site is decontaminated. Only then
can final closure be carried out (22). A
small bacterial load can, in individual cases,
be accepted. In isolated cases, ruptures of
the right ventricle may occur during these
interventions. As long as no connective tissue plate has formed retrosternally, which
as a general rule occurs after 6-8 weeks,
fixation of the sternum or residual part of
the sternum must be carried out.
According to our experience, restabilization
of the sternum is therefore absolutely necessary, dependent on when the heart operation is performed, to prevent mechanical
traumatization of the mediastinal structures, in particular of the right ventricle.
This may happen due to:
- continuos spreading infection;
- sharp ends of the sternum;
- increased or decreased intrathoracic
pressure;
- adhesions between the sternum and the
heart.
Complete rewiring need not be carried out,
about 3-4 cerclages or cords being sufficient
to prevent injury to the heart or vessels (4,
22, 27, 30, 31).
This is true for both planned revisions as
well as for reconstructions. Therefore, in
the VAC phase for every revision restabilization must be carried out once again. If
as a result of severe osseous destruction
secure refixation is not possible, rewiring
according to Robicsek (4) may be considered. Further stabilization during VAC is
achieved by means of a vacuum.
As a result of selective refixation only, the
mediastinum can be well drained with
maximum safety and reliability. Mobilization of the patient is thus possible in an uncomplicated fashion.
An accidental loss of vacuum as a result of
detachment of the foil, disconnection of the
VAC system or excessive mobilization can
be corrected unproblematically without exposing the patient to the danger of a ruptured ventricle.
We dispense with covering the medial
structures with compresses or membranes
soaked in paraffin without refixation of the
sternum. If the interval from the heart operation to treatment of the mediastinitis is
longer than 6-8 weeks and if there is an
adequate retrosternal connective tissue
layer, refixation of the sternum becomes
unnecessary.
In these cases, in consultation with the patient, stabilization of the sternum can be
achieved by means of pseudarthrosis.
239
240
As a result of the myocutaneous plastic coverage, good additional stability is achieved
by the muscle portions “growing into” the
bony residual cavities (9, 11).
5.
6.
CONCLUSION
7.
In our own patient collective, all patients
showed a deep infection with the involvement of the sternum and/or the mediastinum. After an average of three debridements
of the soft tissues and the sternum with the
removal of the avital areas by means of sequesterectomy and partial resections the
sternum lay relatively denuded.
From our point of view it is of immense
importance to cover the remaining osseous
sternum with well-perfused tissue and not
adding protracted, secondary wound healing with the resulting presternal dysfunctional scar tissue. Furthermore, further
stabilization is achieved as a result of myoplastic coverage.
The therapeutic algorithm, radical surgical
debridement, VAC therapy serving as a conditioning and bridging treatment with additional myoplastic reconstruction, proved to
be a save and reliable technique for treating
deep sternal infections with good results,
no recurrent infections and a justifiable
risk (22).
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
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19.
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49: 179-86.
3. Sjögren J, Malmsjö M, Gustafsson R, Ingemansson R. Poststernotomy mediastinitis: a review of conventional surgical
treatments, vacuum-assisted closure therapy and presentation of the Lund University Hospital mediastinitis algorithm. Eur J Cardiothorac Surg. 2006; 30: 898-905.
4. Robicsek F, Fokin A. Complications of Midline Sterno-
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El Oakley RM, Wright JE. Postoperative mediastinitis: classification and management. Ann Thorac Surg. 1996; 61:
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62: 1479-83.
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Pairolero PC, Arnold PG, Harris JB. Long-term results of
pectoralis major muscle transposition for infected sternotomy wounds. Ann Surg. 1991; 213: 583-9.
Argenta LC, Morykwas MJ. Vacuum-assisted closure: a
new method for wound control and treatment: clinical experience. Ann Plast Surg. 1997; 38: 563-76.
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Wackenfors A, Gustafsson R, Sjögren J, et al. Blood flow
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negative pressure wound therapy (NPWT) after poststernotomy mediastinitis - a single center experience with 54
patients. J Cardiothorac Surg. 2009; 4: 5.
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Cardiovasc Surg. 2011; 59: 15-20.
Jurkiewicz MJ, Bostwick J 3rd, Hester TR, et al. Infected
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wound infections. Plast Reconstr Surg. 1994; 93: 1208-14.
25. Daigeler A, Falkenstein A, Pennekamp W, et al. Sternal
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flap for chest wall repair after complete resection of infected sternum. Ann Thorac Surg. 1995; 60: 1028-32.
29. de Fontaine S, Devos S, Goldschmidt D. Reduction mammaplasty combined with pectoralis major muscle flaps for
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30. Abu-Omar Y, Naik MJ, Catarino PA, Ratnatunga C. Right
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Cite this article as: Ennker IC, Ennker JC. Management of sterno-mediastinitis. HSR Proceedings in Intensive Care and
Cardiovascular Anesthesia 2012; 4 (4): 233-241
241
gifZ\\[è^j
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EXPERT OPINION
!"#$%&"'()
Acute and chronic thoracic aortic
disease: surgical considerations
M. Loebe, D. Ren, L. Rodriguez, S. La Francesca, J. Bismuth, A. Lumsden
Methodist DeBakey Heart & Vascular Center, The Methodist Hospital, Houston, Texas
ABSTRACT
Acute thoracic aortic aneurysm is one of the most life-threatening vascular disorders recognized to date. The
majority of these aortic ruptures rapidly end in mortality, with 50% of patients suffering death before reaching the hospital. Thus, acute management through surgical intervention is often indicated, especially in cases of ascending aortic rupture. Physical examination is critical in making the diagnosis, as clinical signs and
symptoms often vary depending on the location of the dissection. Clinicians should have a low threshold for
including thoracic aortic dissection in their differential diagnosis, especially when a patient presents with
acute onset chest or back pain. In this report, we discuss the different categories of aortic dissections and the
current treatment modalities for each. These include endovascular aortic repair, which has become a viable
treatment modality in certain cases of type B dissection. Offering a less invasive approach, the technique
known as thoracic endovascular repair currently affords a treatment option to a patient population who
would have otherwise been deemed non-surgical candidates. Hybrid thoracic endovascular aortic repair
has also become a pertinent surgical technique, and successful outcomes have been demonstrated when it
is employed to repair ascending aortic aneurysms. We also describe our Acute Aortic Treatment Center,
a rapid multicentric triage system for the management of acute aortic pathologies, which has resulted in
significant improvements in patient outcomes.
Keywords: aortic aneurysm, aortic dissection, DeBakey classification system, Stanford classification system, Acute
Aortic Treatment Center.
INTRODUCTION
Acute thoracic aortic aneurysm (TAA) is
the most life-threatening vascular disorder
recognized to date. Aortic ruptures have an
80% mortality rate, with 50% of patients
suffering death before reaching the hospital
(1). The risk of death from untreated type
A dissections is 25%, 50%, 75%, and 90%
Matthias Loebe, MD, PhD
6550 Fannin Street, Suite 1401
Houston, TX 77030
at 24 hours, 2 days, 1 week and 1 month,
respectively (2). Due to their severity, all
acute ascending aortic dissections require
emergency surgery in order to prevent aortic rupture and death.
HISTORY
Death of King George II of Great Britain
On the morning of October 25, 1760, King
George II started his usual 6:00 a.m. routine, drank a cup of hot chocolate and went
to his closet stool. After a few minutes, his
243
M. Loebe, et al.
Figure 1 - The DeBakey
and Stanford classification
systems for aortic dissection. Reprinted with permission from the Cleveland
Clinic Foundation.
244
valet heard a loud crash and entered the
room to find the king on the floor. The
king was lifted on to his bed and Princess
Amelia, his daughter, was sent but, when
she reached him, he was dead. The postmortem examination of King George II
of Great Britain (1683-1760) revealed an
aortic aneurysm and rupture of the right
ventricle. This examination was carried
out by the king’s physician, Frank Nicholls
(1699-1778), who was the first person to
document a case of aortic dissection (3).
The man on the table devised the surgery
In 1955, Dr. Michael E. DeBakey and colleagues reported the first series of patients
with aortic dissections successfully treated
with primary surgical repair (4) employing
techniques that are still widely used today
(5, 6). Fifty years later, on the late afternoon of December 31, 2005, Dr. DeBakey,
then 97 years old, was alone at home preparing a lecture when a sharp pain ripped
through his upper chest, between his shoulder blades, and then moved into his neck.
“It never occurred to me to call 911 or my
physician,” Dr. DeBakey said, adding: “As
foolish as it may appear, you are, in a sense,
a prisoner of the pain, which was intolerable. You’re thinking, what I could do to
relieve myself of it. If it becomes intense
enough, you’re perfectly willing to accept
cardiac arrest as a possible way of getting
rid of the pain” (7). But when his heart
kept beating, Dr. DeBakey suspected that he
was not having a heart attack. It was these
symptoms, and his years of experience, that
lead him to suspect he was having dissecting aortic aneurysm. Two months later, he
would undergo aortic aneurysm surgical
intervention, and became the oldest patient
ever to benefit from such a repair.
Classification
There are two gold-standard classification
systems for aortic dissections: the DeBakey
system and the Stanford system. They differ in that the former is based on the anatomy, and the latter on management of the
patient (Figure 1). In general, Stanford
Thoracic aortic disease
type A dissections affect the ascending
root, while type B affects the descending
aorta. Type A is a surgical emergency, in
contrast to type B, which is less lethal and
can be treated conservatively with medical therapy and concomitant endovascular
intervention. As described in a publication based on the International Registry of
Acute Aortic Dissection, the less invasive
endovascular treatment has been shown
to provide better in-hospital survival in
patients with acute type B dissection (8).
However, findings such as leaking, rupture
or end organ compromise are indications
for surgical intervention.
Clinical presentation
Sudden onset of severe chest pain is the
typical presenting feature of aortic dissections. This pain may be excruciating, sharp,
ripping, or tearing in nature. Nearly 90%
of patients report acute chest pain. Anterior chest pain is typically seen in type A
dissections, while type B dissections present back and abdominal pain. Acute aortic
dissections can be misdiagnosed as acute
myocardial infarction when the dissection
extends into the coronary ostia. Clinical
signs resembling those of acute myocardial
ischemia (i.e. Electrocardiography changes
and elevated cardiac biomarkers) are often
discovered on initial workup.
Less common symptoms that may be seen
in acute aortic dissection include congestive heart failure (7%), syncope, cerebrovascular accident, ischemic peripheral
neuropathy, paraplegia, cardiac arrest and
sudden death (9). Acute aortic dissection
into the pericardium resulting in tamponade is the second most common cause
of death in acute aortic dissection (10).
Complications of aortic insufficiency occur in one-half to two-thirds of ascending
aortic dissections and may lead to congestive heart failure or cardiogenic shock.
The most common cause of death in type
B dissection is mesenteric ischemia (11).
Respiratory complications that can also be
observed include tachypnea, dyspnea and
orthopnea due to mass effects on the tracheobronchial tree. Cerebral ischemia and
stroke syndromes are the most common
central nervous system effects of proximal
acute aortic dissection, occurring 5-15% of
the time (12).
Risk factors
The most common medical risk factor for
aortic dissection is hypertension (70-90%),
especially if uncontrolled (2). The highest
incidence of aortic dissection occurs in
individuals who are 50 to 70 years of age.
Two-thirds of patients with acute aortic
dissections are male. Patients with type B
dissections tend to be older than type A
patients (mean age of 66 vs. 61 years, respectively) (13, 14). Additionally, of the
dissections occurring in females younger
than age 40, about half occur during pregnancy (typically in the third trimester or
early postpartum period) (15).
It has been shown that 50% of patients
younger than 40 years of age who suffer an
aortic dissection have a Marfan-like phenotype (11). Having a congenital bicuspid
aortic valve increases the risk of aortic dissection by 10 times compared to the risk
of the general population and is a factor in
14% of all cases (11). Additionally, individuals who have undergone aortic valve
replacement for insufficiency are at particularly high risk. Interestingly, 18% of individuals who present with an acute aortic
dissection have a history of cardiac surgery
and/or catheterization (11).
Diagnostic imaging
Plain chest X-ray is abnormal in most patients suspected of having an acute aortic
dissection and is abnormal (i.e. shows mediastinal widening) in about 90% of cases
(16). Double aortic knob sign, irregularity
245
M. Loebe, et al.
Figure 2 - Acute Aortic
Treatment Center Passway. Image reproduced
with permission from
Davies MG, Lumsden AB.
Acute Aortic Treatment
Center. Methodist DeBakey
Cardiovasc J. 2011; 7: 8-10.
OR = operating room;
ER = emergency room;
EMT = emergency medical technician;
CV = cardiovascular;
ICU = intensive care unit;
CT = computed tomography.
246
of the aortic contour, tracheal displacement, and pleural effusion are all nonspecific findings that should prompt more
precise investigation. Helical computed
tomography (CT) is the most commonly
utilized study for making the diagnosis
of acute aortic dissection because of its
relatively quick turnover, broad availability, and high sensitivity/specificity for this
complication. Diagnostic CT provides detailed information about the location and
extent of anatomic anomalies, and can be
further enhanced with contrast employment.
The benefit of magnetic resonance angiography (MRA) is that it provides enhanced
details of the aorta, arch vessels and aortic valve insufficiency without the use of
ionizing radiation or iodinated contrast
material. However, MRA is best used for
monitoring patients with chronic aortic
dissection and in postoperative followup. Transthoracic/transesophageal echocardiography (TTE/TEE) is a relatively
non-invasive test that may provide a safer
method for confirming or excluding aortic
dissection. TTE/TEE also gauges the severity of certain valve problems and contributes valuable information by detecting
involvement of the coronary arteries, communications between true/false lumens,
and aortic regurgitation.
Acute aortic treatment center
Key elements that have significantly reduced mortality from acute aortic syndromes include rapid patient transportation, employment of a dedicated
multi-disciplinary team and subsequent
prompt diagnosis and intervention (Figure
2) (17).
As pioneers in the treatment of acute aortic manifestations, the Methodist DeBakey
Heart & Vascular Center has developed the
Acute Aortic Treatment Center (AATC)
to rapidly triage and treat acute aortic disease. The AATC has resulted in a 30% increase in volume, a 64% reduction in time
to definitive treatment and a reduction in
intensive care unit time, while maintaining clinical efficacy despite significantly
more acute admissions (18). Our experi-
Figure 3 - Dacron graft
repair of ascending and descending aortic dissection.
Reprinted from Journal
of Vascular Surgery, Volume 44 Issue 4, Wei Zhou,
Michael Reardon, Eric K.
Peden, Peter H. Lin, Alan B.
Lumsden, pages 688-693,
Copyright 2006, with permission from Elsevier.
ence with the AATC has demonstrated its
clinical relevance and we will continue to
develop this system to optimize outcomes
in the future (18).
Surgical repair
Aortic dissection involving the ascending
aorta or proximal aortic arch (DeBakey
type I and II or Stanford type A) requires
immediate surgical repair. A Dacron graft
may be used to replace portions of the ascending aorta or total aortic arch (Figure
3). If the patient’s aortic valve is competent, David’s valve-sparing aortic root replacement has shown clinical efficacy and
is currently the most favorable technique.
The major advantage is the avoidance of
anticoagulation. The modified Bentall procedure has promising short- and long-term
results for patients with severely dilated
aortic root and valves (19).
Patients with DeBakey type III and Stanford type B dissection receive surgical intervention only in certain conditions. The
majority of these patients can be treated
conservatively with blood pressure con-
trol. Surgery or endovascular therapies are
performed when there are complications
from the aortic dissection, such as rupture, organ or limb perfusion dysfunction,
a large size aneurysm (>5 cm), or rapid
expansion in aneurysm diameter during a
1-year period.
Open surgical repair of distal thoracic aortic dissection is often associated with unacceptably high risks of paralysis (4.2%),
fatal bleeding (2%), stroke (2.5%), and renal failure (3.5%) (14). While spinal cord
ischemia and renal failure warrant the
most consideration, the most important
methods are: cerebrospinal fluid drainage,
left heart bypass, perfusion of renal arteries with 4°C crystalloid solution, and reattachment of segmental arteries, especially
between T8 and L1 (20).
Endovascular repair
Although medical therapy is still the first
line treatment in patients with type B dissection and aneurysm, thoracic endovascular aortic repair (TEVAR) has emerged as
an acceptable treatment. TEVAR offers a
247
M. Loebe, et al.
supports a paradigm shift, with TEVAR
(introduced in 1991) emerging as the preferred therapy for all patients presenting
with descending aortic rupture (23, 24).
A large meta-analysis study of centers
across the United States has demonstrated
improved shorter perioperative outcomes
when compared to open aortic repair
(OAR) procedures, despite a targeted older
patient population. The same study also
showed that TEVAR is associated with a
shorter total length of stay and less complications. However, TEVAR did have significantly greater hospital charges when
compared to OAR (25).
248
Figure 4 - Schematic representation showing
arch and visceral debranching inflow from the
ascending aorta. Reprinted with permission from
the Department of Cardiovascular Surgery, Methodist DeBakey Heart & Vascular Center.
minimally invasive approach to aneurysm
stabilization and repair, while avoiding
the increased prothrombotic state associated with thoracotomy and clamping of the
proximal aorta (21).
The procedure involves the insertion of
a presized endograft that is secured under
real time fluoroscopic imaging. Successful
endograft repair depends on accuracy of
deployment and landing zone, and that the
aneurysm is absent of any residual leaks.
Clinical follow up should confirm complete
retraction and thrombosis of the aneurysm
sac, and the patient should be free of any
signs and symptoms (22). Current data
Hybrid thoracic endovascular aortic repair
Aneurysms involving the ascending aorta
and arch have traditionally been treated
with open surgery involving cardiopulmonary bypass with or without deep hypothermic circulatory arrest. In some cases,
a staged elephant trunk procedure is required. TEVAR can be limited by inadequate proximal and distal landing zones.
A novel technique for repair of these aneurysms has emerged using debranching
or hybrid TEVAR. Unlike TEVAR, which
is performed by a vascular surgeon, hybrid
TEVAR is performed by a multidisciplinary
team of vascular and cardiac surgeons. For
this technique, aortic arch debranching
is required before the placement of endografts (26, 27). Debranching is performed
for two fundamental reasons:
1) to provide an appropriate landing zone
for thoracic stent grafts;
2) to ensure ongoing perfusion of the supra-aortic vessels (Figure 4).
The technical advantages of the hybrid
procedure is that it again eliminates the
need for aortic clamping, while allowing
direct visualization and preparation of the
proximal landing zone for subsequent TEVAR. The debranching can be completed
via right anterior minithoracotomy, which
avoids the morbidity and complications
associated with sternotomy (28). Despite
preliminary success with the procedure,
there are no objective studies that have
established superiority over conventional open approach and further studies are
merited (29).
CONCLUSION
Improvements in diagnostic protocol,
surgical technique and guideline-driven
management have changed the way acute
and chronic aortic manifestations are approached and treated. Crucial to patient
management has been the employment
of advanced and timely diagnostic imaging procedures, such as helical CT, MRA,
and TEE. Prompt surgical intervention for
Stanford type A aortic dissection and proximal thoracic aortic aneurysm has demonstrated excellent survival with acceptable
morbidity and is currently the gold-standard treatment.
However, hybrid procedures employing
branched/fenestrated endografts, as well as
percutaneous aortic valves, have emerged
as relevant alternatives to traditional surgical intervention. They have demonstrated
significant improvement in mortality and
morbidity.
Moreover, these procedures have been employed as a bridge to subsequent TEVAR
and should be considered in high-risk
older patients. In closing, logistical and
technological advances have significantly
improved patient outcomes in patients
suffering acute abdominal aneurysms. We
look forward to further investigating the
benefits of employing a designated care
team and center, as our experience with
the AATC has shown higher success rates
afforded by rapid diagnosis and management.
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and after initiation of an acute aortic treatment center. J
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Cite this article as: Loebe M, Ren D, Rodriguez L, La Francesca S, Bismuth J, Lumsden A. Acute and chronic thoracic aortic
disease: surgical considerations. HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4 (4): 243-250
Acknowledgements: The authors thank Amanda Hodgson, PhD, for critical reading of the manuscript.
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ORIGINAL ARTICLE
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Cardiovascular tissue
banking in Europe
T.M.M.H. de By1, R. Parker1, E.M. Delmo Walter2, R. Hetzer1,2
1
Foundation of European Tissue Banks, Berlin; 2Deutsches Herzzentrum Berlin.
ABSTRACT
Introduction: In the past 50 years, human cardiovascular tissue allografts, also called homografts, have been
implanted into patients with different valvular diseases. The use of these allografts and the number of cardiovascular tissue banks and their respective techniques increased. We conducted a survey to establish the
quantity of allografts processed, and issued by, European tissue banks. The survey also included the collection
of other relevant statistics.
Methods: In 2011, the Foundation of European Tissue Banks collected data from 19 different cardiovascular
tissue banks in 11 European countries.
Results: From 2007 to 2010 the data show a decrease in the number of hearts received, from 1700 to 1640 in
18 tissue banks; the average number of hearts received for cardiovascular tissue processing decreased from 113
to 91. The number of heart valves issued for transplantation increased from 1272 in 2007 to 1486 in 2010. The
average rate of discard because of microbiological contamination was 20.7%, while 4.2% of the grafts were not
used because of positive serology. Half of the tissue banks issued arterial grafts, while 3 banks also issued veins
and pericardium. An overview of decontamination methods shows considerable methodological differences
between 17 cardiovascular tissue banks.
Conclusions: From the experience in Europe, it can be concluded that cardiovascular tissue banks have an
established place in the domain of cardiovascular surgery. The statistics show fluctuating data concerning the
demand for human cardiovascular allografts and methodological questions. There is room for growth and improvement with respect to validation of decontamination methods.
Keywords: cardiovascular tissue, tissue donor, tissue bank, homograft, ross operation, discard rate, microbiology,
contamination, decontamination, serology, validation.
INTRODUCTION
In the early 1960s Ross and Barratt-Boyes
introduced the use of human allograft cardiac heart valves, or homografts, into clinical practice (1, 2).
In 2012 the 50th anniversary of the first socalled Ross operation was celebrated.
The Ross operation encompasses implantaCorresponding author:
Theo M.M.H. de By
tion of a pulmonary autograft in the aortic
position, while an allograft is transplanted
in the pulmonary position.
Ever since, there has been a need to store
available donor grafts, so that they can be
prepared, stored in a tissue bank, and used
for implantation, either in elective or in
emergency patients. From the end of the
sixties and into the eighties tissue banks
were founded all over Europe (3).
In the same period studies about the techniques and successes of homograft implantation in larger series of patients were published, followed in the nineties by studies
251
T.M.M.H. de By, et al.
252
which covered more than a decade (4-14).
Because, over time, they were the only successful biological heart valve prostheses beside the mechanical ones, the results were
very satisfactory.
The advantages were clear: a low rate of
thromboembolic events, thus avoiding a
lifetime of anticoagulation therapy. In addition, their hemodynamic properties were
superior to those of mechanical valves, especially those available in the early 1960s
and 1970s.
As time went by, it became clear that the
availability and cardiectomy techniques to
obtain cardiovascular tissues were a problem as suitable donors were recipients of
heart transplants, organ donors whose
hearts were not accepted, or donors who
were autopsied and their relatives had
agreed to their tissues being used (15).
In the last 20 years, the European cardiovascular tissue banks have invested a great
deal of finances and effort in improving the
safety and quality of their tissue banking
methods and facilities. Issues such as donor
selection, validation of testing methods, the
improvement of sterility systems and clean
rooms were addressed.
Regulations based on Directives (16) of the
European Union became law in all member
states.
The Foundation of European Tissue Banks
initiated a survey to obtain an assessment
and quantification of the situation in the
field of cardiovascular tissue banks, after
implementation of the European Directives into national legislation. This study
presents the results of that survey.
METHODS
In 2011, questionnaires were sent out to 30
cardiovascular tissue banks, 18 of which
completed and returned them. One cardiovascular tissue bank had started its activities in early 2011; hence no data could be
reported as yet. Three additional questionnaires were received after the statistical
analysis was closed, and these data are not
included.
The data received were accumulated and
statistically stratified. Ranges and means
were calculated and tabulated giving insight into the level of activities of these
cardiovascular tissue banks. Percentages of
detected positive serology were assembled,
and a break-down of microbiological contamination as the reason for discarding
tissue should yield information on the reasons for tissues being discarded during the
process.
Ethical approval was waived given the observational and retrospective design of the
study. No data from individual donors and
patients were used in this study.
Table 1 - General statistics.
2007
2008
2009
2010
Number of banks providing data
16
17
18
18
Number of countries
8
8
9
10
Number of hearts received
1700
1685
1663
1640
% of grafts issued for grafting
39.3
45
46.8
46.9
Average number of hearts received
113
120
111
91
10-312
4-334
9-307
17-262
Range of hearts received
issuing grafts, similar differences are observed. As shown in Table 2, the number of
grafts issued ranges from 4 to 243. The statistics in Table 2 confirm that the demand
for pulmonary grafts is about twice as high
as the demand for aortic valves: 67% of all
grafts issued were pulmonary valves.
The data provided by the 18 cardiovascular
banks show that, in 2010, exporting of tissues to other countries was done by 7 banks,
with the proportion varying from 1% to 72%
of the annual number of processed grafts.
Table 3 provides insight into the information
with respect to donors. The average donor
age ranges from 40 (in 2007) to 42 in 2010.
Fifty-seven percent of the hearts originated
from organ donors of whom the heart could
not be transplanted, 28% from non-organ
donors (those who become donors after an
extended period of cardiac arrest, and are
RESULTS
The statistics in Table 1 are based on the
assumption that every heart received in
the cardiovascular tissue banks provided
two grafts. Out of 18 tissue banks, 11 had
registered the number of donor reports
rather than the hearts actually received in
the bank. In these 11 tissue banks, 67% of
the donors reported resulted in the receipt
of a heart in the bank. Table 1 shows that
from the total of 1640 hearts received by
18 tissue banks in 2010, only 46.9% provided suitable grafts; hence the discard rate
is 53.1%.
The cardiovascular tissue banks show a
considerable difference in their activities:
while in 2010 the highest number of grafts
received was 262, the smallest bank processed only 17 grafts. When it comes to
Table 2 - Heart valves issued per year.
2007
2008
2009
2010
Aortic valves
462
508
514
505
Pulmonary valves
810
953
938
981
Mean number of aortic valves issued
36
34
34
34
Mean number of pulmonary valves issued
62
73
59
61
4-95
10-84
5-85
4-79
16-184
15-226
7-223
17-243
2007
2008
2009
2010
40
40
41
42
Death to cardiectomy criterion range in hrs.
Death to cardiectomy in reality, range in hrs
2-48
2-48
2-48
2-48
3-18
4-16
4-14
5-18
Death to cardiectomy, average hrs in reality
8
8
7
11
Death to excision criterion range in hours
Death to excision in bank in reality, range
24-72
24-72
24-72
24-72
12-44
13-45
17-42
18-43
Death to excision, average hours in reality
24
24
24
24
Range of aortic valves issued
Range of pulmonary valves issued
Table 3 - Donor information.
Mean age (yrs)
253
254
thus unsuitable as organ donors) and 15%
were retrieved from so called “domino donors”. Domino donors are people who undergo a heart transplantation, and whose
native heart may still have valves that are
transplantable as tissue grafts.
The criteria for the time between cardiac
arrest and cardiectomy, as observed by
the tissue banks in this study, ranged from
2 to 48 hours. In reality, the average time
until cardiectomy was between 8 hours in
2007, and 11 hours in 2010. After receipt
in the tissue bank, the valvular grafts are
excised from the heart and decontaminated. Also here, the criteria differed greatly
between the banks and the time varied
from 18 hours to 72 hours, while the average number of hours in practice was 24.
Table 4 shows the reasons for discarding
donor tissue. In 2010, 45.3% of the tissue
Table 4 - Heart valve discards in 2010, average % of all cardiovascular banks.
Heart valve discards in 2010, average % of all cardiovascular banks
Not selected because of:
% of received hearts
Medical history
32.7
Serology
4.2
Microbiology
Bacteria
10.7
Multi resistant bacteria
0.4
Fungi
3.2
Not specified
0.1
Suspected
0.35
Total microbiology
5.9
Morphology
35.8
Technical
7.3
Other or unknown reasons
7.8
Table 5 - Different decontamination methods in 17 European cardiovascular tissue banks.
Duration
Valve bank
Antibiotics
Barcelona, BST Cefoxitin
Antibiotics:
concentration
240 µg/mL
of culture
Temperature
24hrs
5ºC (2-8ºC)
mg/L
240
Vancomycin
50 µg/mL
50
Polymyxin B
120 µg/mL
120
Clindamycin
(Lyncomicin)
100 µg/mL
100
Amphotericin B
5 µg/mL
Barcelona, TSF Penicillin
50 U/ml
Medium
5
24 hrs
o
o
5 C (+/- 3 C)
50 U
Vancomycin
50 µgr/ml
50
Streptomycin
50 µgr/ml
50
Amphotericin B
in medium
500ml RPMI
10 µgr/ml
w/o L-glutamine
10
RPMI
Bad
Oeynhausen
Berlin
Bristol
Brussels
Cracow
London
Linz
Lund
0.024% (m/V)
Lincocin
0.012% (m/V)
120
Colistin
0.0099% (m/V)
99
Vancomycin
0.005% (m/V)
Amikacin
1.2 mg/2 ml Syringe
18-24 hrs
6o C
Mefoxitin
255
240
50
18-24 hrs
5o C (+/- 3o C)
21-24 hrs
22o C
Metrodinazol
1.2 mg/2 ml Syringe
Flucytosin
3.0 mg/2 ml Syringe
Vancomycin
1.2 mg/2 ml Syringe
Ciprofloxacin
1.2 mg/2 ml Syringe
Amphotericin
0.05 mg/ml
Ciprofloxacin
0.20 mg/ml
200
Vancomycin
0.05 mg/ml
50
Gentamicin
in Hanks’ BSS
4.00 mg/ml
4000
Lincocin
120 µg/ml
Vancocin
50 µg/ml
50
Polymixine B
in medium 199
124 µg/ml
124
M199
Gentamicin
100 mg/ml
100
RPMI
48 hrs
24 hrs
4o C
4° C
50
120
Vancomycin
50 mg/ml
50
Clindamycin
120 mg/ml
120
Colistin
100 mg/ml
100
Ampicilin +
Sulbactam
200 mg/ml
200
Amphotericin B
25 mg/ml
Cefuroxime
250 ug/ml
25
24 hours
o
37 C
250
Gentamicin
80 ug/ml
80
Ciprofloxacin
200 ug/ml
200
Vancomycin
500 ug/ml
500
Colistin
1000 IU/ml
1000 UI
Amphotericin
100 ug/ml
Amphotericin B
125 µg/ml
Gentamicin
600 µg/ml
600
Metronidazol
600 µg/ml
600
Ciprofloxacin
150 µg/ml
150
Vancomycin
600 µg/ml
Amphotericin
250 ug/ml
Ketokonazol
100 ug/ml
HANKS
100
24 +/- 2 hrs
+ 4° C
125
600
24 hours
5C
(+/- 3o C)
o
250
100
RPMI
256
Milano
Colistin
200 ug/ml
200
Vancomycin
500 ug/ml
500
Gentamicin
Polimyxine B
sulphate
500 ug/ml
100 µg/ml in
RPMI1640 medium
50 µg/ml in
RPMI1640 medium
240 µg/ml in
RPMI1640 medium
120 µg/ml in
RPMI1640 medium
500
Vancomycin
Cefoxitin or
Cefotaxime
Lincomycin
Oxford
Paris
Prague
Rotterdam
Treviso
24 hours
4° C
100
50
240
120
Amikacin
1g/L
18-24 hrs
20 - 30o C
Cefuroxime
500 mg/L
500
Vancomycin
1g/L
1000
Timentin
3.2g/L
3200
Polymixin B
10,000,000 iu/L
1000
Nystatin
1440,000iu/L
Vancomycin
500 mg/L
Gentamicin
320 mg/L
320
Clindamycin
In RPMI
medium
600 mg/L
600
Amikacin
0.1 mg/ml
Ampicilin +
Sulbactam
0.2 + 0.1 mg/ml
Cefoperazon
0.2 mg/ml
200
Fluconazol
0.1 mg/ml
100
Amphotericin B
0.1 for NHBD
in medium 199
0.1
100
Amikacin
(as sulphate)
0.6 mg/mL
Vancomycin
0.6 mg/mL
600
Ciprofloxacin
(as lactate)
0.15 mg/mL
150
Metronidazole
0.6 mg/mL
600
Flucytosine
1.5 mg/mL
1500
Vancomycin
100 mg/ml of
RPMI 1640 medium
18/24 h
24 hrs
4°C
20 - 30° C
M199
500
RPMI
100
200+100
5-6 hours
72 hrs
37oC
+ 4° C
600
100
Polimyxine
100 mg/ml (1.000.000 IU/ml) of RPMI 1640 medium
100
Ceftazidima
240 mg/ml of RPMI 1640 medium
240
Lincomycin
120 mg/ml of RPMI 1640 medium
120
RPMI
Warsaw
Tazocin
(Piperacillin/
Tazobactam)
0.5 mg/ml
Gentamicin
0.05 mg/ml
Nystatin
2 500 j./ml
Vancomycin
0.5 mg/ml
24 hrs
20o C
(+/- 2o C)
257
500
50
50
Barcelona, BST = Banco de Sang y Tejidos; Barcelona, TSF = Transplant Services Foundation; RPMI = Roswell Park Memorial Institute;
HANKS’ BSS = Hanks Balanced Salt Solution; M199= Medium 199; NHBD = Non Heart Beating Donors.
grafts had to be discarded. In many cases
there was more than one reason for not
accepting the heart, or its tissue grafts, for
transplantation.
In 32.7% of the cases the reason for discard
was that there were contraindications for
transplantation of the tissue in the donor’s
medical history. During processing 35.8%
of the cardiovascular tissue was found to
be unsuitable because of its morphology.
In 17.65% and 4.2% of the cases, respectively, microbiology or serology test results
were a reason not to accept the grafts for
transplantation.
Technical and unknown reasons were responsible for 7.3% and 7.8%, respectively,
of the discards. Table 5 gives an overview of
decontamination methods in 17 cardiovascular tissue banks. Substantial differences
can be observed in the number of hours
during which the tissue banks culture the
tissue to detect and/or eliminate microorganisms; the range is 5-72 hrs. Also, the
temperature under which incubation takes
place shows a large variety: from 4o C to
37o C. The banks use 25 different antibiotics in many different concentrations.
In Table 6 a breakdown of other tissues
provided by the banks in this study shows
that pericardium, arteries and veins are
processed alongside valvular allografts.
DISCUSSION
The level of activity in cardiovascular tissue banks is determined by the numbers of
donors. This study shows that the range of
Table 6 - Other tissues issued.
Other tissues issued
2007
2008
2009
2010
3
3
3
3
19%
18%
17%
17%
tissues
39
50
54
81
banks
7
7
7
9
In % of all banks
44%
41%
39%
50%
tissues
307
305
423
481
banks
3
3
3
4
in % of all banks
19%
19%
17%
22%
tissues
245
229
314
286
banks
Pericardium
Arteries
Veins
in % of all banks
258
donor hearts received in 18 banks varied
from 1640 in 2010 to 1700 in 2007.
As the number of hearts received represents only 67% of the number of donors
referred, it may be worthwhile to analyze
the reasons why the hearts of 33% of the
reported donors were eventually not allocated to the tissue bank. By eliminating
factors preventing the donation from materializing, banks would be able to increase
their activity.
On the other hand the statistics document
that in 2010 45.3% were not suitable for
transplantation and had to be discarded.
Better donor screening beforehand, and a
more effective process from cardiectomy
to excision and for decontamination in the
bank are three factors which could decrease
this high number of discards.
This study shows in statistics what cardiovascular tissue bankers have known for a
long time, that the demand for pulmonary
valves is about twice as high as the demand
for aortic valves: 66% of all grafts are pulmonary valves.
Although this study does not extend to the
use of grafts, the literature shows that for
many centers the pulmonary valve is the allograft of choice in congenital as well as in
acquired cardiac diseases (11).
The activity of the banks varies from processing less than 20 to 262 donor hearts in
2010. One has to wonder about the routine
capabilities of personnel as well as about
the optimal use of the investment and costs
of maintenance of a class A laboratory.
The donor age (Table 3) has gradually increased from an average of 40 in 2007 to 42
years in 2010. As the average age in the European population increases, the donor age
increases accordingly. Some cardiovascular
tissue banks receive hearts from organ donors only. The reason is twofold:
1) some authorities forbid the use of nonorgan donors;
2) to set up a cardiectomy team on a 24/365
basis requires additional organizational constraints and investments which
some banks wish to avoid.
Most cardiovascular tissue banks strive to
increase the volume of available tissue. The
dependency on the receipt of organ donor
and domino donor hearts brings them into
a vulnerable position. The need for additional cardiovascular grafts could be compensated by an effort to set up a non-organ
donor program.
The discard because of morphology can
hardly be avoided. However, the differences in decontamination methods, use of antibiotics and their concentrations, as well
as temperature should be a subject to cause
concern in the cardiovascular tissue banks
participating in this study.
In 2010, a conference of these tissue bankers and their microbiologists was organized by the Foundation of European Tissue Banks. Substructuring and validation
methods were exchanged, and some arguments were proven to be right. At that conference, and from the questionnaire in this
study, no adverse events were reported by
any of the participating tissue banks.
While most of the cardiovascular tissue
banks in this study concentrate on the processing and distribution of the “classic” homograft heart valves, nine banks showed
activities with respect to processing tissues
such as arteries, veins and pericardium. Table 6 clearly shows an increase in the distribution of arterial grafts. Correspondence
with different tissue bank representatives
revealed that the demand for arterial grafts
is growing throughout Europe. While veins
are used in access surgery (shunts), pericardium serves as patching material to
bridge larger gaps of deficient tissue during
cardiothoracic operations.
The numbers of these tissues issued over
the period 2007-2010 also show a considerable increase.
CONCLUSION
For the first time since the start of the clinical use of human allogeneic heart valves,
data from a number of European cardiovascular tissue banks could be accumulated.
Statistics with respect to numbers, discard
and use of cardiovascular tissue provide insight into the magnitude of their activities as
well as into some of the parameters they use.
First of all, looking at the number of tissue
grafts issued for transplantation, one can
conclude that the demand for tissues has
not decreased during the period of 4 years
encompassed in this study. Apparently the
demand increased by 16.8%, from 1272 to
1486, over a 4-yearperiod.
The results show that cardiovascular tissue
bank activities have remained relatively
stable over the years, though the number
of donors has somewhat decreased (3.5%).
While the demand for pulmonary grafts
still increased from 810 to 981 (21.1%),
only 505 aortic grafts were issued in 2010.
What happens with all the aortic grafts
which are not issued is a logistical as well
as an ethical question.
In order to cope with the persistently high
demand for pulmonary grafts and arteries,
those cardiovascular tissue banks which do
not retrieve hearts from non-organ donors
should seriously consider initiating such a
donor program.
Although not clinically proven, studies
show that stem cell techniques may eventually contribute to the quality and availability of human heart valves, yet none of
the cardiovascular tissue banks indicated
that they are in any way involved in stem
cell research.
The differences in accepted time lapses
from death to cardiectomy, and from cardiectomy until excision of the valves and
further processing find their origin in viewpoints with respect to quality and safety. A
consensus between the tissue banks con-
tributing to this study should be based on
data with respect to the potential loss of
tissue quality starting at cardiac arrest and
measured over time.
As there are very large methodological differences with respect to microbiology testing, incubation and decontamination of
cardiovascular tissue between the 17 contributing tissue banks, there is a necessity
to validate procedures and room for improvement (17-19). This survey shows an
increased demand for other tissues, which
may be worth further exploration.
After all, where alternatives seem to fail
or are absent, it is the task of tissue banks
to satisfy the clinical demand for tissue
grafts.
REFERENCES
1. Ross DN. Homograft replacement of the aortic valve. Lancet 1962; 2: 487.
2. Barratt-Boyes BG, Lowe JB, Cole DS, Kelly DT. Homograft replacement for aortic valve disease. Thorax 1969;
20: 489.
3. Parker R. An international survey of allograft banks. Cardiac Valve Allografts, Science and Practice. Darmstadt:
Steinkopf, New York: Springer, 1997; 5-9.
4. Clarke DR, Campbell ON, Hayward AR, Bishop DA. Degeneration of aortic valve allograft in young recipients. J
5. Yankah AC, Pasic M, Klose H, et al. Homograft reconstruction of the aortic root for endocarditis with periannular
abscess: a 17-year study. Eur J Cardiothorac Surg 2005; 28:
69-75.
6. Willems TP, van Herwerden LA, Steyerberg EW, et al.
Subcoronary implantation or aortic root replacement for
human tissue valves: sufficient data to prefer either technique? Ann Thorac surg 1995; 60: 83-6.
7. Musci M, Weng Y, Amiri A, et al. Homograft aortic root replacement in native or prosthetic active infective endocarditis: 20-year single center experience. J Thorac Cardiovasc
Surg 2010; 139: 665-73.
8. Bekkers JA, Klieverik LM, Raap GB, et al. Re-operations
for aortic allograft root failure: experience from a 21-year
single-center prospective follow-up study. Eur J Cardiothoracic Surg. 2011; 40: 35-42.
9. Mokhles MM, van de Woestijne PC, de Jong PL, et al. Clinical outcome and health-related quality of life after rightventricular-outflow-tract reconstruction with an allograft
conduit. Eur J Cardiothorac Surg. 2011; 40: 571-8.
10. Parker R, Randev R, Wain WH, Ross DN. Storage of heart
valve allografts in glycerol with subsequent antibiotic sterilisation. Thorax 1978; 33: 638-45.
11. O’Brien MF, Stafford G, Gardner M, et al. The viable preserved allograft aortic valve. Journal of Cardiac Surgery
1987; 2 (Suppl.): 153-67.
12. Carr-White GS, Kilner PJ, Hon JK, et al. Incidence, loca-
259
260
13.
14.
15.
16.
17.
tion, pathology and significance of pulmonary homograft
stenosis after the Ross operation. Circulation 2001; 104:
116-20.
Yankah CA, Yacoub MH, Hetzer R. Cardiac Valve Allografts, Science and Practice. Darmstadt: Steinkopf, New
York: Springer, 1997.
Barrat-Boyes BG. Aortic allograft valve implantation: freehand or root replacement? J Card Surg 1994; 9: 196-7.
Jashari R, Goffin Y, Vanderkelen A, et al. European homograft bank: twenty years of cardiovascular tissue banking
and collaboration with transplant coordination in Europe.
Transplant Proc 2010; 42: 183-9.
EU Directives 2004/23/EC, 2006/17/EC and 2006/84/EC
Jashari, R, Vanhoeck B, Fan Y, Improving the cardiectomy
at the European Homograft Bank (EHB). The Postmortem
Donation of Cardiovascular Tissues, Forschungsergebnisse
aus dem Institut für Rechtsmedizin der Universität Hamburg, Band 21, 105-08.
18. Contamination of human cardiovascular tissues. Origin, treatment and literature. Petit P, de By TMMH, The
Postmortem Donation of Cardiovascular Tissues, Forschungsergebnisse aus dem Institut für Rechtsmedizin der
Universität Hamburg, Band 21, 109-34.
19. Bactericidal effects of superoxide solution (SOS); proof of
principle. Van den Bogaerdt AJ, Petit P, van Wijk M, Bogers
AJ. The Postmortem Donation of Cardiovascular Tissues,
Forschungsergebnisse aus dem Institut für Rechtsmedizin
der Universität Hamburg, Band 21, 139-40.
Cite this article as: de By TMMH, Parker R, Delmo Walter EM, Hetzer R. Cardiovascular tissue banking in Europe. HSR
Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4 (4): 251-260
We thank the cardiovascular tissue banks of Bad Oeynhausen, Barcelona (TSF and BST), Berlin, Brussels (EHB), Cordoba,
Cracow, London, Linz, Liverpool, Lund, Milano, Oxford, Paris, Rotterdam, Treviso, Valencia, Warsaw and Zagreb for their
contributions.
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ORIGINAL ARTICLE
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Tricuspid valve surgery
C.A. Mestres1, G. Fita2, V.M. Parra3, J.L. Pomar1, J.M. Bernal4
1
Department of Cardiovascular Surgery, Hospital Clínico. University of Barcelona. Barcelona, Spain; 2Department
of Anesthesiology, Hospital Clinico, University of Barcelona, Barcelona, Spain; 3National Chest Institute and School of Medicine,
University of Chile, Santiago Chile; 4Department of Cardiovascular Surgery, Hospital Universitario Valdecilla, University
of Cantabria, Santander, Spain
ABSTRACT
Introduction: The tricuspid valve has been taken as a non-critical valve in terms of acute or late mortality
in a number of conditions. Tricuspid functional regurgitation is a cause of late operations with an increased
morbidity. A number of techniques have been described and used in clinical practice in the past forty years
and include simple suture techniques and the use of support for annuloplasty with the use of different types of
prosthetic rings. The experience accumulated over the years indicates that tricuspid annuloplasty is mandatory
to improve late results, which are superior, in general, to replacement of the valve.
Methods: The role of echocardiography in defining surgical planning, intraoperative results and follow-up
is reviewed as echocardiography is a fundamental tool in cardiac surgery. Surgery for isolated lesions of the
tricuspid valve has not received much attention and herein we report the results of the follow-up of a limited
series of patients undergoing isolated tricuspid surgery.
Results: The correlation between echocardiographic measurements and surgical measurements was confirmed and was helpful at the time of the confirmation of repair (r=0.53). Forty-seven patients (18 repair,
29 replacement) underwent isolated surgery. Results of isolated tricuspid repair seemed to be superior when
compared to those of tricuspid replacement. Survival was 20.7% for tricuspid valve replacement (N=18) and
50% for tricuspid valve repair (N=29) (p=0.04). Freedom from reoperation was 94.4±5.4% for repair and
67.3±12.1% for replacement (p= 0.0011).
Conclusions: The tricuspid valve continues to be a surgical challenge.
Keywords: tricuspid valve, tricuspid regurgitation, valve repair, echocardiography.
Presented at the 3rd Expert forum of the Roland Hetzer International Cardiothoracic and Vascular Surgery Society on the
INTRODUCTION
The tricuspid valve (TV) is usually considered a forgotten valve. This is because the
other cardiac valves are more frequently
addressed in the scientific literature (1, 2).
Dr. Carlos-A. Mestres MD, PhD, FETCS
Department of Cardiovascular Surgery
Hospital Clínico, University of Barcelona
Villarroel, 170 - 08036 Barcelona, Spain
The aortic and mitral valves are involved
in rheumatic disease showing gross changes after an acute or chronic inflammatory
reaction. The diseases of the TV frequently
present in the form of regurgitation, which
is functional as a consequence of pulmonary congestion. The gross anatomy of the
TV is seldom seriously affected as to require replacement regardless of the disease (3).
Replacement of the TV is, in fact, an uncommon clinical operation in current times
(4) as repair conveys good long-term results
261
C.A. Mestres, et al.
262
(5-8). In the specific case of rheumatic valve disease it is clear that survival is better
and reoperation less frequently required
when the valve is repaired (9, 10).
On the other hand, the mechanisms of TV
normal and abnormal function are well
known for decades (11) and what is clear is
that right ventricular contractility is a key
component of TV function and that left-sided lesions do influence on TV function as
well. Considering all of the above, it might
be of interest to briefly review current concepts and therapeutic attitudes towards a
diseased TV.
Dealing with the tricuspid valve. The TV has
been approached from different perspectives but the underlying accepted philosophy
of repair. It is known that functional TV
regurgitation is more amenable for repair
than organic involvement and it can be said
that a myriad of possibilities have already
been tested in clinical practice with success.
Non-prosthetic repair. Bicuspidization of the
TV can be considered a very early type of
repair without the use of prosthetic material. Their results sustained the test of time
as reported by Kay et al. (12); however, there were always concerns on residual tricuspid regurgitation that were addressed at a
later stage when comparisons were made
with prosthetically-supported repairs (13).
For TV repair, de De Vega selective and
adjustable suture-based repair is credited
as one of the most popular valve operations in the past four decades since it was
first reported in 1972 (14). Technical tips
are simple and this operation is a truly reproducible one as it has been shown in the
literature. Some concerns exists about somewhat unpredictable results (13). But forty years later this technique continues to
be widely used. There are a number of factors that might influence on its results that
have recently been addressed by Yilmaz et
al. (15) and on which De Vega has briefly
summarized for practical purposes (16).
A number of modifications of the De Vega
procedure have also been described and clinically tested (17-19). Some focused on the
segmental nature of the repair (19, 20) on
top of the semicircular extension including
the anteroseptal and posteroseptal commissures. The concept of vanishing annuloplasty was introduced trying to eliminate
foreign materials; after such a vanishing
annuloplasty, the benefit of semicircular repair will remain (21, 22). The truth with
regards actual effectiveness might be related, like in the setting of the mitral valve,
on which of the multiple components of the
tricuspid valve complex bears the responsibility of the substrate for regurgitant lesions. This is well described by Navia et al.
in a retrospective analysis of multiple types
of supported and non-supported repairs of
the TV (23). The essence of non-prosthetic
repair is based on preservation of valvular
mechanism while maintaining the physiological flexibility of the annulus; prosthetic material is not required; there are less
chances of damage to the conduction tissue
and also important that these techniques
are easy, fast to perform and cheap.
Prosthetic repair. Since the early independent work by Carpentier et al. (24) and Duran et al. (11, 25) the concept of supported
TV repair using different types of prosthetic rings has developed rapidly. There are
currently more than 20 different ring designs in the market for mitral and tricuspid
repair. Ring repair follows the same basic
statements accumulated in the literature
and that are contemplated in guidelines,
namely that here is evidence that TV regurgitation associated with dilatation of the
tricuspid annulus should be repaired, that
tricuspid dilatation is an ongoing process
that may progress to severe TR if untreated and that annuloplasty of the TV based
on tricuspid dilatation improves functional
status independent of the degree of regurgitation (26, 27).
Correction of annular dilatation, remodelling the shape of the annulus, improvement
of coaptation between leaflets during systole and stabilization of repair over time are
the main goals of ring repair. The controversy about which type and shape is still
active. If a ring has to be opened or closed,
flexible or rigid, permanent or degradable is
still a matter of controversy that is likely to
be active for years. The contribution by Navia et al. on the comparisons of techniques
that include any type of support or the lack
of it is of importance as defines success as
related to the valve component influencing
on the lesion (23).
What seems clear is that TV ring annuloplasty tends to confer stability to the repair
that positively influences long-term outcomes (10, 28). Furthermore, there is a trend
towards a reduced number or reoperations.
This is serious information and may favour the use of rings in clinical conditions
in which annular dilatation plays a major
role. Other than the discussion on the type
and shape of the ring, materials could play
a role in future decisions in specific groups
of patients.
As with vanishing sutures (22), the recently
introduced concept of a biodegradable ring
addresses important issues like the preservation of the potential for growth of the mitral annulus, which is of particular impact
in pediatric population, the avoidance of
synthetic material with a speculated lesser
risk of endocarditis, the lack of anticoagulation during the first three postoperative
months and an associated easy implantation technique (29). On the questions: is
the fibrous tissue induced by the ring capable of allowing for the natural growth of the
valve orifice in children, hence preventing
valves stenosis over time? and is the fibrous
tissue capable of resisting against the tensile stretch of the dilated annulus?, recent
experience confirms that the biodegradable ring does not restrict annulus growth
without impact on valve function (30).
No action. The lack of action is another way
to deal with the TV. As stressed by De Vega
in his recent editorial (16), the TV has been
approached in different ways for more than
forty years and there still are some doubts
on specific issues. Perhaps one of the most
important questions still under debate is
if clinically silent TV regurgitation must
be address when surgery is performed on
the mitral valve. As stated in the guidelines
(26,27) this is a problem in which decisions
are usually not easy. However, the contribution by Yilmaz et al. in which 699 patients were retrospectively analyzed (15),
has been instrumental in defining that,
perhaps, those cases with non-significant
TV regurgitation should not need repair
when left-sided surgery is performed. In
the words of the authors this actually means that a selective approach is preferred.
METHODS
Echocardiography is likely to be the most
important tool in cardiology in modern times. It is an almost non-invasive technique
giving an enormous amount of information
on morphology and function of the cardiac
valves and the myocardium. This is of particular importance at the time of surgery
where transesophageal echocardiography
(TEE) helps in three important issues:
1) confirming lesions immediately before
the procedure;
2) in assessing the quality of a given repair
or the myocardial function at the end of
the operation;
3) during the postoperative period before
discharge to disclose the presence of pericardial effusion and to evaluate eventual failures or dysfunctions of any cardiac structure. This applies to all types
of cardiac defects and its surgical correction regardless of the etiology (31).
263
264
In the case of the TV, intraoperative TEE
introduces a quality factor as accurate measurements may help in determining the
type of an eventual repair. Up to what extent the right ventricular function or the
annulus diameter will be instrumental in
a successful outcome could be a matter of
discussion but it seems that the more accurate measurements the higher the success
of the repair.
In recent times we have conducted a preliminary study in which the degree of tricuspid regurgitation, right ventricular contractility, the dimensions of the right heart
cavities, diameter of the tricuspid annulus
in mm in mid-systole have been measured.
As TEE is a routine, choosing specific views
addressing the TV is summarized in the following: mid-esophageal four-chamber view
with colour-Doppler mapping, mid-esophageal right ventricular inflow and outflow
tracts and short-axis transgastric tricuspid
valve view.
Using this methodology, the aim was to
evaluate if the preoperative estimates of
the tricuspid ring in mm using TEE were
confirmed with the measurements at surgery with the right atrium opened. For this
measurement study and the analysis of the
long-term follow-up of patients who underwent isolated tricuspid surgery, ethical
approval was waived given the observational and retrospective design. The observers
performed three measurements on TEE
with the patient hemodynamically stable.
Measurements at operation were taken
between the antero-posterior and the antero-septal commissures.
RESULTS
In this early series of 59 patients with a
mean age of 63.9 years, the correlation
between echocardiographic measurements
and surgical measurements was confirmed
and was helpful at the time of the confirmation of repair (r=0.53).
Isolated tricuspid valve surgery with normal
functioning left side. The end-stage rheumatic heart valve disease. It is clear today that
rheumatic valve disease is a well known
heart condition which is anecdotal in the
so-called developed countries but is still the
most common cause of heart disease in the
world.
When the tricuspid valve is involved the
prognosis of the disease is worse (32-34).
Isolated tricuspid rheumatic valve disease
is infrequent; due to this, clinical results of
isolated tricuspid valve disease when appears with normal functioning left side valves
are not known in detail (35).
This is due to the scarce information available opposite to tricuspid regurgitation later
after left side valve repair or replacement,
which entails a high risk and very bad prognosis (36).
This lack of information prompted us to
review a series of patients over a long period of time that underwent surgery for isolated TV disease. Between 1977 and 2010,
47 patients with a mean age of 59 years
(19% male, 81% in atrial fibrillation) underwent repair (18/38.3%) or replacement
(29/61.7%). Preoperative characteristics
are shown in Table 1. Tricuspid repair consisted in a De Vega annuloplasty (N=8),
Duran flexible ring annuloplasty (N=10)
with associated commissurotomy in 2. Tricuspid valve replacement was performed
with a mechanical valve in 14 and with a
tissue valve in 15 patients. Follow-up was
complete in 97.8% of the patients with a
mean follow-up of 16 years (3 months - 33
years).
Survival at the abovementioned followup is 20.7% for TV replacement (N=18)
and 50% for TV repair (N=29) (p=0.04)
(Table 2). Freedom from reoperation is
94.4±5.4% for repair and 67.3±12.1%
for replacement ( p=0.0011).
Table 1 - Preoperative characteristics of patients with isolated tricuspid surgery.
Age
TV Replacement
TV Repair
N=29
N=18
265
p value
59.9±13.6
62.3±5.5
Range
21-76
53-76
n.s.
Female
23 (79.3%)
15 (83.3%)
n.s.
Weight
59.6±11.5
66.5±10.3
n.s.
Height
157.3±6.5
160.9±7.4
n.s.
Body surface area
24.1±4.4
25.7±3.5
n.s.
Atrial fibrillation
27 (93.1%)
14 (77.8%)
n.s.
Cardiac index
PA Sistolic pressure
2.0±0.7
2.1±0.3
n.s.
43.3±13.7
42.7±11.3
n.s.
Pulmonary capillary pressure
26.5±2.4
21.7±4.2
<0.0011
Left ventricular EF
57.8±10.1
54.3±11.7
n.s.
3.57
3.55
n.s.
Previous TV surgery
Repair
Replacement
7 (24.1%)
4 (13.8%)
2 (11.1%)
-
Previous CPB operations
One
Two
Three
11 (37.9%)
9 (31.0%)
2 (6.9%)
6 (33.3%)
2 (11.1%)
-
NYHA class III
7 (24.1%)
12 (66.7%)
NYHA class IV
19 (65.5%)
4 (22.2%)
Mean TV regurgitation
0.04
n.s.
0.002
PA = pulmonary artery; TV = tricuspid valve; EF = ejection fraction; CPB = Cardiopulmonary Bypass; NYHA = New York
Heart Association.
Table 2 - Intra-, postoperative and follow-up data.
TV Replacement
TV Repair
p value
CPB time
79.9±42.8
75.7±45.7
Ischemic time
21.8±23.1
64.5±48.8
n.s.
Mortality
Cardiac
Bleeding
Neurologic
8 (27.6%)
6
1
1
-
0.0002
0.01
Late mortality
Cardiac
Valvular
Unknown
Reoperation
Thromboembolism
Hemorrhage
Malignacy
Others non cardiac
15 (51.7%)
2
1
7
1
1
1
2
9 (50.0%)
3
1
1
2
1
1
n.s.
TV = tricuspid valve; CPB = Cardiopulmonary Bypass
266
DISCUSSION
CONCLUSION
In these case series we noted that the correlation between echocardiographic measurements and surgical measurements was confirmed and was helpful at the time of the
confirmation of repair (r=0.53). Furthermore, results of isolated tricuspid repair seemed to be superior when compared to those of tricuspid replacement. Survival was
20.7% for TV replacement and 50% for
TV repair. Freedom from reoperation was
94.4±5.4% for repair and 67.3±12.1%
for replacement.
It is clear that this was a small series accumulated over a long period of time and this
may be a cause of controversy when analyzing results in an uncommon situation. However, we understand that isolated tricuspid valve surgery with normal functioning
left side valve occurs after mitral and/or
aortic valve surgery, isolated tricuspid valve
surgery has a high early and late mortality
due to cardiac causes and that tricuspid valve replacement entails a worse result comparing with tricuspid valve repair.
Other than classical repair or replacement
of the TV and exception made of the old approach of simple valvulectomy without valve replacement in specific cases for salvage
as advocated by Arbulu three decades ago
(37), valve transplantation using cryopreserved homografts has been an alternative
to TV replacement is specific subgroups
of patients (38). This has been used by us
mostly in cases of TV infection that required surgical treatment as has been reported
before (39). Some technical modifications
have been introduced over time (40) but
one of the most interesting experiences during the follow-up has been to learn about
the eventual possibility of repairing a transplanted mitral valve into the TV position
(41). Of course that should be taken as a
surgical anecdote but it may be useful in
isolated cases.
The tricuspid valve is still a challenging
surgical problem. There is variability in approach and techniques. Echocardiography
is fundamental in planning and execution.
Specific subsets of patients are at high risk
of morbidity and mortality.
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15. Yilmaz O, Suri RM, Dearani JA, et al. Functional tricuspid
regurgitation at the time of mitral valve repair for degenerative leaflet prolapse: the case for a selective approach. J
16. De Vega NG. Yesterday’s future: the gap between where we
are now and where we were supposed to be. Eur J Cardio-
thorac Surg. 2012 Epub ahead of print. PMID: 22659896.
17. Cabrol C. Valvular annuloplasty. A new method. Nouv
Presse Med 1972; 1: 1366.
18. Imamura E, Ohteki H, Koyanagi H. An improved de Vega
tricuspid annuloplasty. Ann Thorac Surg 1982; 34: 710-3.
19. Antunes MJ. Segmental tricuspid annuloplasty: a new technique. J Thorac Cardiovasc Surg 1990; 100: 320-1.
20. Revuelta JM, Garcia Rinaldi R. Segmental tricuspid annuloplasty: a new technique. J Thorac Cardiovasc Surg 1989;
97: 799-801.
21. Bex JP, Lecompte Y. Tricuspid valve repair using a flexible
linear reducer. J Card Surg 1986; 1: 151-9.
22. Duran CM, Kumar N, Prabhakar G, et al. Vanishing De
Vega annuloplasty for functional tricuspid regurgitation. J
23. Navia JL, Nowicki ER, Blackstone EH, et al. Surgical management of secondary tricuspid valve regurgitation: annulus,
commissure, or leaflet procedure? J Thorac Cardiovasc Surg
2010; 139: 1473-82.
24. Deloche A, Guérinon J, Fabiani JN, et al. Anatomical study
of rheumatic tricuspid valvulopathies. Applications to the
critical study of various methods of annuloplasty. Arch Mal
Coeur Vaiss 1974; 67: 497-505.
25. Durán CM, Pomar JL, Cucchiara G. A flexible ring for atrioventricular heart valve reconstruction. J Cardiovasc Surg
(Torino) 1978; 19: 417-20.
26. American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of
patients with valvular heart disease); Society of Cardiovascular Anesthesiologists, et al. ACC/AHA 2006 guidelines
for the management of patients with valvular heart disease:
a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed
in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular
Angiography and Interventions and the Society of Thoracic
Surgeons. J Am Coll Cardiol 2006; 48: 1-148.
27. Authors/Task Force Members, Vahanian A, Alfieri O, et
al. Guidelines on the management of valvular heart disease
(version 2012): the Joint Task Force on the Management of
Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic
Surgery (EACTS). J Cardiothorac Surg. 2012; 42: 1-44.
28. Tang GH, David TE, Singh SK, et al. Tricuspid valve repair
with an annuloplasty ring results in improved long-term
outcomes. Circulation. 2006; 114: 577-81.
29. Kalangos A, Sierra J, Vala D, et al. Annuloplasty for valve
repair with a new biodegradable ring: an experimental study. J Heart Val Dis 2006; 15: 783-90.
30. Mrowczynski W, Mrozinski B, Kalangos A, et al. A biodegradable ring enables growth of the native tricuspid annulus. J Heart Valve Dis 2011; 20: 205-15.
31. Mestres CA, Fita G, Azqueta M, Miró JM. Role of echocardiogram in decision-making for surgery in endocarditis.
Curr Infect Dis Rep 2010; 12: 321-8.
32. Raja SG, Dreyfus GD. Surgery for functional tricuspid regurgitation: current techniques, outcomes and emerging
concepts. Expert Rev Cardiovasc Ther 2009; 7: 73-84.
33. Raja SG, Dreyfus GD. Basis for intervention on functional tricuspid regurgitation. Semin Thorac Cardiovasc Surg
2010; 22: 79-83.
34. He J, Shen Z, Yu Y, et al. Criteria for determining the need
for surgical treatment of tricuspid regurgitation during mitral valve replacement. J Cardiothorac Surg 2012; 7: 27.
35. Bernal JM, Pontón A, Diaz B, et al. Combined mitral and
tricuspid valve repair in rheumatic valve disease: fewer reoperations with prosthetic ring annuloplasty. Circulation
2010; 121: 1934-40.
36. Bernal JM, Pontón A, Diaz B, et al. Surgery for rheumatic
tricuspid valve disease: a 30-year experience. J Thorac Cardiovasc Surg 2008; 136: 476-81.
37. Arbulu A, Holmes RJ, Asfaw I. Surgical treatment of intractable right-sided infective endocarditis in drug addicts:
25 years experience. J Heart Valve Dis 1993; 2: 129-37.
38. Pomar JL, Mestres CA. Tricuspid valve replacement using
a mitral homograft. Surgical technique and initial results. J
Heart Valve Dis 1993; 2: 125-8.
39. Pomar JL, Mestres CA, Pare JC, Miro JM. Management of
persistent tricuspid endocarditis with transplantation of
cryopreserved mitral homografts. J Thorac Cardiovasc Surg
1994; 107: 1460-3.
40. Miyagishima RT, Brumwell ML, Eric Jamieson WR, Munt
BI. Tricuspid valve replacement using a cryopreserved mitral homograft. Surgical technique and initial results. J Heart Valve Dis 2000; 9: 805-8.
41. Mestres CA, Castellá M, Moreno A, et al. Cryopreserved
mitral homograft in the tricuspid position for infective endocarditis: a valve that can be repaired in the long-term (13
years). J Heart Valve Dis 2006; 15: 389-91.
Cite this article as: Mestres CA, Fita G, Parra VM, Pomar JL, Bernal JM. Tricuspid valve surgery. HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4 (4): 261-267.
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IMAGES IN MEDICINE
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268
Is flow really continuous in last
generation continuous flow Ventricular
Assist Devices? A comparison between
HeartMate II and HeartWare HVAD
G. Melisurgo, M. De Bonis, M. Pieri, T. Nisi, S. Silvetti, A. Zangrillo, F. Pappalardo
Cardiovascular and Thoracic Department, Università Vita-Salute San Raffaele, Milan, Italy
Continuous-flow ventricular assist devices
(VADs) are the standard of care for implantable mechanical circulatory support (1).
However, some doubts have been raised
based on the experience with cardiopulmonary bypass about possible adverse effects
of non-pulsatile flow on organ function (2).
Pulsatile perfusion might have a beneficial
effect on peripheral organs probably through
an action on systemic vascular resistance
and on microcirculation, as a result of less
endothelial damage and normalization of nitric oxide (NO) release. However, long-term
use of newer generation continuous-flow devices has resulted in similar improvements
in organ function (3). Actually, blood flow
through continuous-flow VADs is not really
continuous, since it depends on the differential pressure between the left ventricle
and the ascending aorta at a certain VAD
speed (4). During support, the failing native heart continues to function and it generates a variation in intracardiac pressures
along the cardiac cycle: during systole an
increase in left ventricular pressure will be
transmitted to the pump and will transiently increase the VAD flow, generating some
degree of arterial pulsatility. Potapov et al.
(5) first detected a pulsatile flow in patients
Giulio Melisurgo
Cardiovascular and Thoracic Department
Via Olgettina, 60 - 20132 Milan, Italy
implanted with DeBakey continuous-flow
device. Moreover, intermittent aortic valve
opening, either spontaneous or generated
by periodical reduction of VAD speed, has a
major role in maintenance of pulsatility. Recently, Potapov et al. (6) also demonstrated
that long-term mechanical circulatory support with continuous-flow devices does not
adversely influence arterial wall properties
of the end-organ vasculature: in this histological study, no differences in arterial wall
characteristics were found between tissue
samples from liver, kidney, coronary arteries, and brain between patients treated with
continuous-flow devices and patients with
pulsatile-flow (PF) devices. No data is available whether these concepts apply differently to rotary and centrifugal pumps. In order
to evaluate the degree of arterial pulsatility
in patients implanted with newer generation continuous-flow VAD, we performed
Doppler measurements of flow parameters
in two patients, one patient implanted with
HeartMate II (Thoratec, Pleasanton, CA)
axial pump (patient A) and one implanted
with HeartWare HVAD (HeartWare Inc, Miami Lakes, FL) centrifugal pump (patient B).
Doppler studies were performed 3 months
after implantation in both patients, with a
comprehensive examination of both central
and peripheral vascular vessels (common
carotid arteries, middle cerebral arteries,
upper and lower limb arteries). For each
Doppler measurement pulsation index (PI)
Continuous flow Ventricular Assist Devices?
269
Figure 1 - Pulsatile flow in internal carotid artery
in patient A (A) and in patient B (B) and in common femoral artery in patient A (C) and B (D).
Figure 2 - M-mode imaging of aortic valve in patient A (A) and patient B (B) showing any systolic
valve opening during the cardiac cycle.
was calculated (PI: [Vmax-Vmin]/Vmean).
All data were retrospectively collected by
chart review after local ethical committee
approval, and treated anonymously. In both
patients we found some degree of pulsatility,
which was higher in the peripheral vascular
vessels (mean PI 1,15 in omeral and femoral
arteries in patient A and mean PI 0,86 in patient B) than in the central vessels (mean PI
0,4 in internal carotid and middle cerebral
arteries and mean PI 0,43 in patient B) (Figure 1, Video 1, available at the URL: http://
www.hsrproceedings.org/allegati/video/
hsrp-04-268-s001.mpg). In both patients
simultaneous echocardiographic imaging
of the aortic valve showed no systolic valve
opening (Figure 2, Video 2, available at the
URL: http://www.hsrproceedings.org/allegati/video/hsrp-04-268-s002.mpg), associated with a severe reduction of left ventricular ejection fraction (20% both in patient
A and patient B). The examination was performed in both patients at 90 mmHg mean
systolic blood pressure; the HeartMate II
was running at 9400 revolutions per minute (rpm) and HeartWare HVAD at 2700
rpm. This clinical experience highlights for
the first time the presence of flow pulsatility in both central and peripheral vessels
in patients implanted with last generation
continuous-flow VADs, with similar parameters in axial and centrifugal pumps.
These data add a piece of information on
the physiological adaptation of circulation
after continuous flow pump implantation.
REFERENCES
1. Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart
failure treated with continuous-flow left ventricular assist
device. N Engl J Med. 2009; 361: 2241-51.
2. Ji B, Undar A. An evaluation of the benefits of pulsatile versus nonpulsatile perfusion during cardiopulmonary bypass
procedures in pediatric and adult cardiac patients. ASAIO
J. 2006; 52: 357-61.
3. Kamdar F, Boyle A, Liao K, et al. Effects of centrifugal,
axial, and pulsatile left ventricular assist device support on
end-organ function in heart failure patients. J Heart Lung
Transplant. 2009; 28: 352-9.
4. Slaughter MS. Long-term continuous flow left ventricular
assist device support and end-organ function: prospects for
destination therapy. J Card Surg. 2012; 25: 490-4.
5. Potapov EV, Loebe M, Nasseri BA, et al. Pulsatile flow in
patients with a novel nonpulsatile implantable ventricular
assist device. Circulation. 2000; 102 (Suppl. 3): 183-7.
6. Potapov EV, Dranishnikov N, Morawietz L, et al. Arterial
wall histology in chronic pulsatile-flow and continuousflow device circulatory support. J Heart Lung Transplant.
2012; 31: 1171-6.
Cite this article as: Melisurgo G, De Bonis M, Pieri M, Nisi T, Silvetti S, Zangrillo A, Pappalardo F. Is flow really continuous
in last generation continuous flow Ventricular Assist Devices? A comparison between HeartMate II and HeartWare HVAD.
HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4 (4): 268-269
Source of Support: Nil. Conflict of interest: None declared.
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LETTER TO THE EDITOR
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LETTER TO THE EDITOR
2012 Pandemic Flu
Dear Editor, a new H1N1 pandemic flu is approaching Europe.
In Italy, the results obtained from the “ECMOnet” network, for the centralization of patients with adult respiratory distress syndrome
(ARDS) in structures with extracorporeal membrane oxygenation (ECMO) support, are encouraging (1,2) but far from being exhaustive, mainly
because of the small number of patients treated.
The ECMO technique seems to be successful
(3), and probably represents the turning point
for patients affected by a respiratory failure
considered, until recently, irrecoverable. Moreover, the key role of extracorporeal life support
in severe hemodynamic failure, not responding
to conventional therapy, is already established,
and a more extensive use of ECMO is recommended. Despite the attention that the technique has received during the previous Italian
pandemic, many physicians do not know the
criteria for patients centralization and therapy
establishment. This could lead to an higher
than expected failure rate due to late or missed
patients centralization.
More efforts are therefore needed to establish the
enrollment criteria and to spread their knowledge among clinicians involved in patients’
recruitment. We would be very grateful if you
could publish the enrollment criteria, shared by
your trustworthy board, to publicize this data
among the Italian ICUs. This could help to improve survival of patients with adult respiratory
distress syndrome (ARDS) not only during the
pandemic, but also during the rest of the year.
Federico Emiliano Ghio1, Carlo Serini1,
Luca Ghislanzoni1, Angelo Calini1,
Giacomo Monti2, Federico Pappalardo2,
Alessandra Ponti1 1
Gruppo di Studio e Ricerca in Medicina di Emergenza,
Busnago Soccorso ONLUS, Milan, Italy;
2
Department of Anesthesia and Intensive Care,
Università Vita-Salute San Raffaele, Milan, Italy
Federico Emiliano Ghio
Gruppo di Studio e Ricerca in Medicina di Emergenza
Busnago Soccorso ONLUS - Milan, Italy
Cite this article as: Ghio FE, Serini C, Ghislanzoni L, Calini A, Monti G, Pappalardo F, Ponti A. 2012 Pandemic Flu. HSR
Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4 (4): 271
RESPONSE
The criteria of eligibility
to the extracorporeal treatment
Dear colleagues,
We agree with your analysis and believe that a
higher circulation of the criteria of eligibility to
the extracorporeal treatment, both for the treatment of severe cases of ARDS and for refractory shock, could lead to a greater number of
patients treated and therefore saved.
However we cannot forget the serious economic crisis that part of Europe is suffering, and
the remarkable cut of the financial resources
that seriously limits the possibility to carry out
programs of widespread awareness campaign.
Despite these hard limitations, other initiatives
continue. A web-based interface for information (www.ecmonet.org) is continuously updated. A 24/24 hours and 7/7 days telephone Help-
line (800 – 82 12 29) is always active in Italy
for any kind of information and assistance. In
engaging ourselves to keep alive the interest of
the scientific community and looking forward
to a “consensus conference” that will establish
guidelines, we propose, as follows, the criteria
of inclusion to the extracorporeal therapy.
Pathological Processes Suitable for venousvenous (V-V) ECMO
• Severe pneumonia
• ARDS
• Acute lung (graft) failure following transplant
• Pulmonary contusion
• Others:
- Alveolar proteinosis
- Smoke inhalation
- Status asthmaticus
- Airway obstruction
- Aspiration syndromes
271
F.E. Ghio, et al.
272
Respiratory Indications to V-V ECMO (after considering recruitment maneuvers, conventional or HFO protective lung ventilation,
prone positioning, diuresis or renal replacement therapy for correction of volume overload,
optimization of perfusion including restoration
of oncotic pressure, intravascular volume, and
inotropes). Identify acute reversible pulmonary
injury and select patients early in the course.
• Murray score >3
• PaO2/FIO2 <100 (mm Hg) despite high
PEEP (10 -20 cmH2O) on FiO2 >80%
• Others:
- intrapulmonary right-to-left shunt
(Qs/QT) >30%
- total thoracopulmonary compliance
(CTstat) <30 ml/cmH2O
- Severe hypercapnia with PaCO2 >80 on
FiO2 >90% or pH <7.20
- Maximal medical therapy >48 h
Contraindication to V-V ECMO
Absolute
• Irreversible cardiac or pulmonary disease
• Metastatic malignancy
• Significant brain injury
• Current intracranial hemorrhage
• Major pharmacologic immunosuppression
(absolute neutrophil count <400 )
Relative
• Age >65-70 years, considering increasing
risk with increasing age
• Mechanical ventilation at high settings (FiO2
>90%, Plateau Pressure >30) >7-10 days
• Multitrauma with high risk of bleeding
Pathological Processes Suitable for venousarterial (V-A) ECMO
• Cardiogenic shock: Acute Myocardial Infarction and complications (including: wall
rupture, papillary muscle rupture, refractory ventricular tachycardia or fibrillation)
refractory to conventional therapy including
intraaortic balloon pump
• Post cardiac surgery: unable to wean safely
from cardiopulmonary bypass using conventional supports
• Drug overdose with severe cardiac depression
• Myocarditis
• Early graft failure: post heart/heart-lung
transplant
•
Others:
- Pulmonary embolism
- Cardiac or major vessel trauma
- Massive hemoptysis/pulmonary hemorrhage
- Pulmonary trauma
- Acute anaphylaxis
- Peri-partum cardiomyopathy
- Sepsis with severe cardiac depression
- Bridge to transplant
Cardiac Indications to V-A ECMO (shock
persist despite volume administration, maximal inotropic and vasoconstrictors support,
mechanical ventilation and intra-aortic balloon
counterpulsation - if appropriate -)
• Cardiac index <2 L/min/m2
• Lactate level >50 mg/dl or 5 mmol/L or
Central Venous Oxygen Saturation - ScVO2
<65% with maximum medical management
• Others:
- Systolic blood pressure less than 90 mmHg
- Low cardiac output
Contraindication to V-A ECMO
Absolute
• Unrecoverable heart and not a candidate for
transplant or Ventricular Assist Device (VAD)
• Age >75 years
• Chronic organ dysfunction (Emphysema, cirrhosis, renal failure)
• Prolonged Cardiopulmonary Resuscitation
without adequate tissue perfusion
• Aortic dissection
• Severe aortic valve regurgitation
• Current intracranial hemorrhage
Extracorporeal Cardiac Life Support
(ECLS) – Extracorporeal Cardiopulmonary
Resuscitation (ECPR)
Indications to V-A ECMO include persistent
cardiopulmonary arrest despite traditional resuscitative efforts
ECLS-ECPR Contraindications to V-A ECMO
• Initial rhythm asystole
• Age >80 years
• Chest compressions not initiated within 10
min of arrest (either bystanders or emergency medical team)
• Cardiopulmonary Resuscitation >60 min
before implanting ECMO
• Pre-existing severe neurological disease (in-
Letter to the editor
•
•
•
•
cluding traumatic brain injury, stroke, or severe dementia)
Current intracranial hemorrhage
Malignancy in the terminal stage
Cardiac arrest of traumatic origin with uncontrolled bleeding
Irreversible organ failure leading to cardiac
arrest when no physiological benefit could be
expected despite maximal therapy
Alberto Zangrillo
Professor of Anesthesiology and Intensive Care
Università Vita-Salute San Raffaele, Milan
REFERENCES
1. Pappalardo F, Pieri M, Greco T, et al. Predicting mortality
risk in patients undergoing venovenous ECMO for ARDS
due to Influenza A (H1N1) pneumonia: the ECMOnet
score. Intensive Care Med 2012; In press.
2. Patroniti N, Zangrillo A, Pappalardo F, et al. The Italian
ECMO network experience during the 2009 influenza
A(H1N1) pandemic: preparation for severe respiratory
emergency outbreaks. Intensive Care Med. 2011; 37:
1447-57.
3. Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult
respiratory failure (CESAR): a multicentre randomised
controlled trial. Lancet. 2009; 374: 1351-63.
Cite this article as: Zangrillo A. The criteria of eligibility to the extracorporeal treatment. HSR Proceedings in Intensive Care
and Cardiovascular Anesthesia 2012; 4 (4): 271-273
273
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PAPERS, POSTERS, PRESENTATIONS:
COMMUNICATING THE BIOMEDICAL SCIENCES
!"#$%&"'()
274
Wish you were here!
M. John
Head of Medical Humanities International MD Program, Professor of Biomedical Communication Skills,
Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy
Nowadays, each and every congress speaker should have at least the basic knowledge required to deal with those technical
issues that might occur before and, more
importantly, during the oral presentation.
Whether it is a Mac or a Windows machine, we all have to know which buttons
to press, which switches to flick, and which
adapter cables to use in order to guarantee
a seamless flow of data during our Keynote
or PowerPoint presentations. Radio-frequency remote controls with integrated laser pointers, cable or cordless microphones,
and iPhone or iPod remote slide changers
can all help make our job easier, making us
all seem like extremely professional public
speakers.
Hang on just a moment! What on earth
am I insinuating? On many occasions our
slides have been prepared by one of our
collaborators, and we might not have even
taken the time to look through them before
reaching the congress venue that, more often than not, might mean that we have been
catapulted to the other side of the planet.
The amazing video we wanted to show is
nowhere to be found, and those excellent
images just show up in the slides as blanks.
I am not familiar with this software. I am
Prof. Michael John
Via Olgettina, 48 - 20132 Milan, Italy
not familiar with this hardware. Help! I
need somebody. Help!
Over the hill rides the cavalry, in the form
of the technical assistance team. These
amazing professionals are always present
at congresses, and are, of course, incredibly
helpful when it comes to setting up and
managing our presentations. Of course, on
many occasions we are obliged to send our
presentations to the congress organizers
beforehand, as they need to upload everything onto their server to simplify events
and make sure that everything is, indeed,
uniform and without hitches and glitches
before the congress starts. On other occasions, we arrive at the venue with our personal laptops, or maybe iPads, and need to
connect to the projector in the congress
hall. This too is sometimes not as easy as
it might sound. This is where the technical
team moves in and shows us which buttons
to press on our PC, or which cable adapter
we need for our Mac in order to be ready
for the show.
Let me just give you an example. I have
made one or two presentations in my time,
but several months ago, while attending an
international anesthesiology workshop in
Barcelona (Spain), I ran into one of the finest teams of technical professionals I have
ever had the honor to meet.
We met up for a pre-workshop briefing,
together with the organizers of the meeting, in the hotel where the congress was to
Wish you were here!
be held the next day for a run through of
my Keynote slides. I had no problems with
graphics or animation, and I was not using
anything complex such as videos or moving
images, so everything worked very smoothly. On my request, the team then took me
to visit the room where I would be working. This was all extremely useful, as it is
paramount for any speaker to be familiar
with the environment where the presentation will take place.
After all, you need to know where you will
stand, how the seating is organized, whether or not there is a board where you can
write should needs be, and if you will be
using a microphone or not.
Even in the smallest of rooms, a clip-on
microphone can be very useful. I honestly
did not think I needed one, as I have a welltrained and rather powerful voice. However, the technical crew explained to me the
error of my ways.
A microphone can give you that little boost
that is needed, just to make sure that every-
one in the audience can hear what you are
saying at all times.
Needless to say, next day everything went
extremely well. The remote worked effortlessly, the laser pointer was spot on, and
the aforementioned microphone was perfect. My presentation was a success, and
I thanked the members of the audience
for their attention, and the members of
the technical crew for their invaluable assistance. The next day, just before leaving
the hotel/congress center, I popped in to
the main congress hall where the big postworkshop event was about to start. What I
saw seemed like something from a science
fiction movie. Screens, images, loudspeakers, huge mixer desks etc. In other words,
the technical crew was once again at work
to help make the event a resounding success. It was magnificent!
These professionals are our roadies. Talk to
them. They are there to help us, and make
sure that everything goes smoothly. Do not
take them, or their talents, for granted.
“This is the sixteenth of a series of articles on this topic.
Send any questions to [email protected] who will answer them as part of this column”
275
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FUTURE EVENTS
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276
Calendar for future meetings
Intensive Care, Surgery and Cardiovascular Anesthesia
2012
May 25th-29th. 21st European Conference on General Thoracic
Surgery. Birmingham, UK. E-mail: [email protected]
December 14th-18th. 66th Postgraduate Assembly, New York State
of Anesthesiologists New York NY.
Info: www.nyssa-pga.org
June 1th-4th. ESA Euroanaesthesia Barcelona, Spain.
Info: www.euroanaesthesia.org
December 14th-15th. 5th International Congress: Aortic Surgery
and Anesthesia “How to Do It” Milano, Italy.
Info: www.aorticsurgery.it
June 6th-8th. 28th Annual Meeting of the European Association of
Cardiothoracic Anesthesiologists. Barcelona, Spain.
Info: www.eacta.org - E-mail: [email protected]
2013
January 19th- 23th. Critical Care Congress Society of Critical Care
Medicine San Juan, Puerto Rico.
Info: www.sccm.org/congress
January 20th-25th. 31st Annual Symposium: Clinical Update in
Anesthesiology, Surgery and Perioperative Medicine with
International Faculty and Industrial Exhibits. Marriott Curacao, The Netherlands.
Info: www.clinicalupdateinanesthesiology.org
February 6th-9th. 33rd Annual Cardiothoracic Surgery Symposium
San Diego, CA. February 6 - February 9 2013.
Info: www.crefmeeting.com
February 17-22th. 6th World Congress of Pediatric Cardiology &
Cardiac Surgery. Cape Town, South Africa.
Info: www.aspr.org/Conference
April 4-5th. 2nd Annual Thoracic Anesthesia Symposium, Miami
Florida. Info: www.scahq.org
April 6th-10th. Annual Meeting & Workshops Society of Cardiovascular Anesthesiologists. Miami Beach, Florida.
Info: www.scahq.org
April 18th-20th. INTERCEPT International Course on Extracorporeal Perfusion Technologies Milano, Italy.
Info: www.intercepteurope.org
May 2th-3th. AATS Mitral Conclave New York, NY.
Info: www.AATS.org
May 4th-7th. IARS 2013 Annual Meeting San Diego CA.
Info: www.iars.org
May 4th-8th. 93rd AATS Annual Meeting Minneapolis, MN.
Info: www.aats.org
May 24th-25th. Aortic Surgery Symposium V. Liverpool, UK.
Info: www.aorticaneurysm.org.uk
June 12th-15th. ASAIO 59th Annual Conference.
Info: www.asaio.com
June 21th-24th. Canadian Anesthesiologists Meeting Calgary,
Alberta. E-mail: [email protected]
June 23th-27th. 20th IAGG World Congress of Gerontology and Geriatrics. Seoul, Korea. Info: www.iagg2013.org
August 9th-13th. Adult Multiprofessional Critical Care Review.
Washington, DC. Info: www.sccm.org
September 19th-21th. XX Annual Congress Czech Society of Anesthesiology and Critical Medicine Brno, Czech Republic.
Info: www.csarim2013.cz
October 5th-9th. 26th Annual Conference European Society of Intensive Care Medicine. Paris, France.
October 12th-16th. ASA Annual Meeting. San Francisco, CA.
Info: www.asahq.org
December 13th-17th. 67th Postgraduate Assembley, New York State
of Anesthesiologists. New York, NY.
Info: www.nyssa-pga.org
2014
September 17th-19th. 29th Joint EACTA-ICCVA Meeting Florence
Italy. Info: www.eacta.org
December. 6th International Congress: Aortic Surgery and Anesthesia “How to Do It” Milano, Italy December 2014.
Info: www.aorticsurgery.it
2016
th
nd
August 28 -September 2 . 16th World Congress of Anesthesiologists Hong Kong. Info: www.WCA2016.com
The Journal of Cardiothoracic and Vascular Anesthesia welcomes announcements of interest to physicians, researchers and
others concerned with cardiothoracic and vascular anesthesiology, medicine, pharmacology and related areas. All copies
are reviewed and edited for style, clarity and length. Information is due at least 90 days before the date of publication, and
should be addressed to: George Silvay, M.D., Ph.D., Editor, Professor of Anesthesiology, Department of Anesthesiology,
Mount Sinai Medical Center, 1 Gustave L. Levy Place, Box 1010, New York, NY 10029-6574.
Email:[email protected]
HSR Proceedings
Proceedings in
in Intensive
Intensive Care
Care and
and Cardiovascular
Cardiovascular Anesthesia
Anesthesia 2012,
2011, Vol.
HSR
Vol. 3
4
How to prepare a manuscript for submission to
HSR Proceedings in Intensive Care and Cardiovascular Anesthesia
English language is the only language allowed
for manuscripts submitted to “HSR proceedings in Intensive Care and Cardiovascular Anesthesia” from November 1st 2009. You can
choose between American or British English,
but be consistent.
“HSR proceedings in Intensive Care and Cardiovascular Anesthesia” offers a “fast track” opportunity: we’ll send you an editorial decision within
7 days if you submit a manuscript through email
with the comments of previous reviewers of other
journals who evaluated your paper. If you ask for a
fast track review and send us comments of previous
reviewer you’ll not have to arrange the references
or the layout according to the below cited journal
guidelines.
Manuscripts must be double-spaced on A4 pages.
A margin of at least 3 cm should be provided on
all sides. All type should be 12 points in size. Pages
must be numbered. Word limits are not imposed on
any manuscript types, but all papers should be as
concise as possible.
Please send your manuscript to [email protected]
The Editorial Office will send by e-mail to the corresponding author all communications related to the
status of a submission, including the final decision
and the scheduled date of publication.
Different manuscripts could be submitted to “HSR
proceedings” including: Original articles; Teaching
articles; Brief reports; Reviews; Meta-analyses; Expert Opinions; Editorial; Case series; Letters to the
Editor; Case reports; Images in clinical medicine.
The peer-review process is applied to all submissions, including appraisal by at least 2 peer-reviewers.
COVER LETTER. Please also send us a cover letter addressed to the Editor in Chief. The letter must
include at the end a list of all authors as if for signature. The cover letter must state that the authors
agree with and are responsible for the data presented. The letter should also acknowledge or deny any
potential conflicts of interest.
MANUSCRIPT. Our preferred file type for new
manuscript submissions is a single Microsoft Word
document containing all element of the article except figures. Figures should be sent singularly as
separate files with the manuscript. In the manuscript provide the title of the paper on the first page
(TITLE PAGE); the title should be concise. Also list
the name of each author, including the first name
and the highest graduate degree; the department
and institutional affiliation of each author and the
name, address, telephone number, fax number, and
e-mail address of the author to whom correspondence should be addressed. ABSTRACT. Provide an
abstract of not more than 250 words and without
abbreviations. If possible, it should consist of four
paragraphs, labeled Background, Methods, Results
and Discussion. They should briefly describe, respectively, the problem being addressed in the study,
how the study was performed, the salient results
and what the authors conclude from the results.
The manuscript itself should be possibly divided
into 4 sections: Introduction, Methods, Results, and
Discussion. Please refrain from using automatic reference list software because its features are often
lost during the publication process. Simply insert
the reference number in parentheses in the text (after any punctuation mark) and type the reference
list. References must be numbered with Arabic
numerals and cited in the text in numerical order.
The reference list at the end of the article must also
be in numerical order. Please cite references, tables
and figures in the text in square brackets. Use of
square brackets is allowed only for citation and in
formulae. The list headed “REFERENCES” should
begin on a new page of the main text document and
be double-spaced. Abbreviations for titles of medical periodicals must conform to those used in Index
Medicus (http://www.nlm.nih.gov/tsd/serials/lji.
html). References to abstracts, supplements and letters to editors must be identified as such. Inclusive
page numbers of references are required.
DETAILS. “HSR proceedings in Intensive Care
and Cardiovascular Anesthesia” will consider for
publication suitable articles on all topics related to
intensive care and to anesthesia for cardiac, thoracic and vascular surgery. The aim of “HSR proceedings” is to contribute to the spread of knowledge in
the field of intensive care, emergencies and major
surgical operations.
Manuscripts are examined by members of the editorial staff and then sent to outside reviewers. We encourage authors to suggest the names of possible reviewers, but we reserve the right of final selection.
Communications about manuscripts will be sent
after the review and then the editorial decisionmaking process is complete.
All articles represent the opinion of the authors and
do not necessarily reflect the opinion of the Editor, Editorial Board or Publisher. The Editors and
Publisher deny any responsibility or liability for
statements and opinions expressed by the authors.
Neither the Editor nor the Publisher guarantee,
warrant or endorse any product or service adver-
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278
tised in this publication, nor do they guarantee any
claim made by the manufacturer of such product
or service.
Manuscripts containing original material are accepted for consideration if neither the article nor
any part of its essential substance, tables, or figures have been or will be published or submitted
elsewhere before appearing in “HSR proceedings”.
This restriction does not apply to abstracts or press
reports published in connection with scientific
meetings.
Authors of all types of articles should follow the
general instructions. These guidelines are in accordance with the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals,” published by the International Committee of Medical
Journal Editors at http://www.icmje.org
Papers reporting human experimentation will be
reviewed in accordance with the precepts established by the Helsinki Declaration (http://www.
wma.net/e/policy/b3.htm). Copies of this declaration may also be obtained by writing to the American Medical Association, 515 N State St, Chicago,
IL 60610.
As stated in the Uniform Requirements, credit for
authorship requires substantial contributions to (a)
the conception and design of the protocol or analysis and interpretation of the data and (b) the drafting of the article or critical revision for important
intellectual content. Each author must sign a statement attesting that he or she fulfils the authorship
criteria of the Uniform Requirements. Any change
in authorship after submission must be approved in
writing by all authors.
In appropriate places in the manuscript, please
provide, if applicable, a statement that the research
protocol was approved by the relevant institutional
review boards or ethics committees and that all human participants gave written informed consent.
When reporting experiments on human subjects,
authors should indicate whether the procedures
followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and
with the Helsinki Declaration of 1975, as revised
in 2000. If doubt exists whether the research was
conducted in accordance with the Helsinki Declaration, the authors must explain the rationale for
their approach, and demonstrate that the institutional review body explicitly approved the doubtful
aspects of the study. When reporting experiments
on animals, authors should be asked to indicate
whether the institutional and national guide for the
care and use of laboratory animals was followed. If
photographs of patients are used, either they should
not be identifiable or the photographs should be
accompanied by written permission to use them.
Patients have a right to privacy that should not be
infringed without informed consent. Identifying
information, including patients’ names, initials, or
hospital numbers, should not be published in written descriptions, photographs, and pedigrees unless
the information is essential for scientific purposes
and the patient (or parent or guardian) gives written informed consent for publication. Informed
consent for this purpose requires that a patient who
is identifiable be shown the manuscript to be published. Authors should identify Individuals who
provide writing assistance and disclose the funding source for this assistance. Identifying details
should be omitted if they are not essential. Complete anonymity is difficult to achieve, however,
and informed consent should be obtained if there is
any doubt. For example, masking the eye region in
photographs of patients is inadequate protection of
anonymity. If identifying characteristics are altered
to protect anonymity, such as in genetic pedigrees,
authors should provide assurance that alterations
do not distort scientific meaning and editors should
so note. The requirement for informed consent
should be included in the journal’s instructions for
authors. When informed consent has been obtained
it should be indicated in the published article.
All text, references, figure legends and tables should
be in one double-spaced electronic document (Microsoft Word document).
Figures. Figures should be sent as separate files.
It is allowed to send low-resolution figures for peer
review. Please note that if the manuscript will be
accepted for publication we will ask for high-resolution files of all figures:
! figures containing only lines and/or text (such
as graphs or flowcharts) must have a resolution
of 900 dpi AND a width between 100 and 200
mm;
! figures containing both lines/text and images
(such as mixed figures containing graphs and
images) must have a resolution of 600 dpi AND
a width between 100 and 200 mm;
! figures not containing lines or text (i.e. color or
black and white images) must have a resolution
of 300 dpi AND a width between 100 and 200
mm.
Formats accepted are JPEG (.jpg), TIFF (.tif), PNG
(.png). Images with a resolution of 72 dpi or smaller than 100 mm will not be accepted. Legends for
all figures should be included in the file with the
text (on a new page after the references list) and
should not appear on the figures.
Tables. Tables should be prepared in Microsoft
Word: they should be formatted preferably with the
tabulation command, otherwise as Microsoft Word
tables. Do not submit tables in PDF format or any
graphic format.
References. References must be double-spaced
and numbered consecutively as they are cited. Possibly list all authors when there are four or fewer;
when there are five or more, list the first three, followed by “et al.”.
Abbreviations. Except for units of measurement,
abbreviations are strongly discouraged. Except for
units of measurement, the first time an abbreviation appears, it should be preceded by the words for
which it stands.
Drug names. Generic names should be used. When
proprietary brands are used in research, include the
brand name and the name of the manufacturer in
parentheses after the first mention of the generic
name in the Methods section.
Instructions for submitting a revised manuscript. We require two versions of the revised manuscript, one with “tracked” or highlighted changes
and one without. Please double-space. Include your
response to the reviewers as a separate file.
If a submitted article is accepted for publication,
editorial revisions may be made to aid clarity and
understanding without altering the meaning.
CONFLICT OF INTEREST. Public trust in the
peer review process and the credibility of published
articles depend in part on how well conflict of interest is handled during writing, peer review, and
editorial decision making. Conflict of interest exists when an author (or the author’s institution),
reviewer, or editor has financial or personal relationships that inappropriately influence (bias) his
or her actions (such relationships are also known
as dual commitments, competing interests, or competing loyalties). These relationships vary from
those with negligible potential to those with great
potential to influence judgment, and not all relationships represent true conflict of interest. The
potential for conflict of interest can exist whether
or not an individual believes that the relationship
affects his or her scientific judgment. Financial
relationships (such as employment, consultancies,
stock ownership, honoraria, paid expert testimony)
are the most easily identifiable conflicts of interest
and the most likely to undermine the credibility of
the journal, the authors, and of science itself. However, conflicts can occur for other reasons, such as
personal relationships, academic competition, and
intellectual passion.
“HSR proceedings” expects that all authors acknowledge financial associations with a company
(or its competitor) that makes a product discussed
in the article. Information published in medical
journals helps shape diagnostic and therapeutic decisions. For a journal to be of value, it must publish
authoritative, up-to-date information that is free
of commercial influence. Because relationships between authors and biomedical companies are growing, we want to ensure that the articles we publish
are not influenced by financial interests.
Authors should disclose any financial arrangement
they may have had in the last 3 years or in the foreseeable future with a company whose product is
pertinent to the submitted manuscript or with a
company making a competing product. Such information will be held in confidence while the paper
is under review and will not influence the editorial
decision but if the article is accepted for publication, a disclosure statement will appear with the article. Here are some examples: Dr. “A” reports having served as a consultant to “A1”. Dr. “B” reports
having been paid lecture fees by “B1”, “B2” and
“B3” Drs. “C, D, E” report having received grant
support from “C1” Neither Dr. “F”A nor Dr. “G”
has any financial interest in the patent. Dr. “H”
and Dr. “I” are consultants to “H1” Dr. “L” reports
having received consulting fees from “I1” Dr. “M”
reports having been a member of speakers’ bureaus
sponsored by “M1”
COPYRIGHT. “HSR proceedings” is the owner of
all copyright to any published work. “HSR proceedings” and its licensees have the right to use, reproduce, transmit, derive works from, publish and distribute the contribution, in the “HSR proceedings”
or otherwise, in any form or medium. Authors may
not use or authorize the use of the contribution
without the “HSR proceedings” written consent.
EDITING SERVICES
“HSR proceedings in Intensive Care and Cardiovascular Anesthesia” offers a service of
English language revision and methodological support to authors that wish to publish in
peer-reviewed journals.
For information and tariffs please contact
[email protected]
Please direct any questions to [email protected]
or visit www.hsrproceedings.org/
“HSR proceedings in Intensive Care and Cardiovascular Anesthesia” editorial offices are located in
the Department of Anesthesia and Intensive Care
at 60 Via Olgettina, Milano, Italy 20132, telephone
(+39) 02.26436158, fax (+39) 02.26436152,
email [email protected]
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Full HSR proceedings Vol. 4

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