HEART
LUNG
VESSELS
ISSN: 2282-8419
IN THE NEXT ISSUES
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and
Editors in Chief
Alberto Zangrillo
Roland Hetzer
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Formerly
“HSR Proceedings
in Intensive Care
and Cardiovascular
Anesthesia”
Vol. 6 · N° 3
· 2014
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NO IN
ASSOCIATE EDITORS
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
Marco Ranieri
Università di Torino S. Giovanni Battista Molinette, Torino, Italia
Vol. 6 • N° 3 • 2014
September
Milan, Italy
SECTION EDITORS
Q INTENSIVE CARE
Ludhmila Abrahao Hajjar
University of Sao Paulo, Sao Paulo, Brazil
EDITORS IN CHIEF
Alberto Zangrillo
Università Vita-Salute San Raffaele
Milan, Italy
Roland Hetzer
Deutsches Herzzentrum Berlin, Germany
Q ANESTHESIA
Fabio Guarracino
Azienda Ospedaliera Universitaria Pisana, Pisa, Italia
Q VASCULAR SURGERY
Roberto Chiesa
Università Vita-Salute San Raffaele, Milano, Italia
Q CARDIAC SURGERY
Ottavio Alfieri
Università Vita-Salute San Raffaele, Milano, Italia
Official Journal of
Roland Hetzer International Cardiothoracic
and Vascular Surgery Society
Berlin, Germany
Endorsed by
ITACTA
(Italian Association
of Cardiothoracic Anaesthesiologists)
www.itacta.org
Deutsches Herzzentrum Berlin, Germany
Q PEDIATRIC CARDIAC SURGERY
AND CONGENITAL HEART DISEASES
Eva Maria Javier Delmo Walter
Children‘s Hospital and Harvard Medical School, Boston, MS, USA;
Deutsches Herzzentrum Berlin, Germany
Q TRANSPLANTATION AND IMMUNOLOGY
Paolo Fiorina
Harvard Medical School, Boston, MA, USA
Q CARDIOLOGY
Giuseppe Biondi-Zoccai
Università degli Studi “La Sapienza”, Roma, Italia
Q PEDIATRIC CARDIOLOGY
Brigitte Stiller
Universitaetsklinikum Freiburg, Germany
Publisher
Q ECHOCARDIOGRAPHY
Michele Oppizzi
Università Vita-Salute San Raffaele, Milano, Italia
Q NEW TECHNOLOGIES
Federico Pappalardo
Università Vita-Salute San Raffaele, Milano, Italia
Q IN HOSPITAL EMERGENCIES
Luca Cabrini
Edizioni Internazionali srl
Divisione EDIMES
EDIZIONI MEDICO SCIENTIFICHE - PAVIA
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Università Vita-Salute San Raffaele, Milano, Italia
Q PEER-TO-PEER COMMUNICATION
Michael John
Università Vita-Salute San Raffaele, Milano, Italia
Q IMAGING
Antonio Grimaldi
Università Vita-Salute San Raffaele, Milano, Italia
Q FUTURE EVENTS
George Silvay
The Mount Sinai School of Medicine, New York, NY
Q SOCIAL MEDIA
Laura Pasin
Università Vita-Salute San Raffaele, Milano, Italia
EDITORS
Rinaldo Bellomo
Austin Hospital, Melbourne, Australia
Friedhelm Beyersdorf
Universitätsklinikum Freiburg, Freiburg,
Germany
Elena Bignami
Università Vita-Salute San Raffaele,
Milano, Italia
Giovanni Borghi
Università Vita-Salute San Raffaele,
Milano, Italia
Editorial Secretariat
Lara Sussani
Anesthesia and Intensive Care
Università Vita-Salute San Raffaele
Via Olgettina, 60 - 20132 Milan, Italy
Tel. +39 02 26436158
Fax +39 02 26436152
[email protected]
Tiziana Bove
www.heartlungandvessels.org
IT technical support
Ilic Radice
Aleph s.r.l. - Milan
[email protected]
Director in chief
Paolo E. Zoncada
Registered at the Milan Tribunal
on November 26th 2009 (number 532)
The Journal is indexed, among others, in:
PubMed and PubMed Central
ISSN (ONLINE): 2283-3420
ISSN (PRINTED): 2282-8419
Printed by
Jona Srl
Paderno Dugnano (MI)
Kevin Lobdell
Sanger Heart and Vascular Institute,
Charlotte, NC, US
Carlos Mestres
Hospital Clínico, University of Barcelona,
Barcelona, Spain
Andrea Morelli
Università Vita-Salute San Raffaele,
Milano, Italia
Enrico Camporesi
University of South Florida, Tampa,
Florida
Murali Chakravarthy
University Hospital of Split, Split, Croatia
Università degli Studi “La Sapienza”,
Roma, Italia
Daniela Pasero
Ospedale San Giovanni Battista, Torino,
Italia
Gianluca Paternoster
Massimo Clementi
A.O.R. Ospedale San Carlo,
Potenza, Italia
Dean, Università Vita-Salute San Raffaele,
Milano, Italia
Emanuele Piraccini
Massimiliano Conte
Maria Cecilia Hospital
GVM Care & Research,
Cotignola (RA), Italia
Antonio Corcione
Ospedale “G.B. Morgagni-Pierantoni”,
Forlì, Italia
Jose Luis Pomar
Hospital Clínico, University of Barcelona,
Barcelona, Spain
AORN Dei Colli, V. Monaldi, Napoli
Martin Ponschab
Laura Corno
Trauma Hospital Linz, Linz, Austria
Università Vita-Salute San Raffaele,
Milano, Italia
J. Scott Rankin
Remo Daniel Covello
Università Vita-Salute San Raffaele,
Milano, Italia
Michele De Bonis
Università Vita-Salute San Raffaele,
Milano, Italia
Francesco De Simone
Università Vita-Salute San Raffaele,
Milano, Italia
Vanderbilt University, Nashville, Tennessee,
USA
Marco Ranucci
IRCCS Policlinico San Donato, Milano,
Italia
Zaccaria Ricci
Ospedale Pediatrico Bambino Gesù, Roma,
Italia
Reitze N. Rodseth
Ospedale del Cuore, FTGM, Massa, Italia
Nelson R. Mandela School of Medicine,
University of KwaZulu-Natal, Durban,
South Africa
Juergen Ennker
Stefano Romagnoli
Paolo Del Sarto
Mediclin Heart Institute, Lahr, Germany
Università di Cagliari, Cagliari, Italia
Ospedale Careggi, Firenze, Italia
Laura Ruggeri
Gian Franco Gensini
Università Vita-Salute San Raffaele,
Milano, Italia
Università degli Studi di Firenze, Italia
Anna Mara Scandroglio
Ravi Gill
Università Vita-Salute San Raffaele,
Milano, Italia
Massimiliano Greco
Università Vita-Salute San Raffaele,
Milano, Italia
EDIZIONI MEDICO SCIENTIFICHE - PAVIA
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Research Institute, Hamilton, Ontario,
Canada
Maria Grazia Calabrò
University Hospital Southampton NHS
Foundation Trust, Southampton, UK
Edizioni Internazionali srl
Divisione EDIMES
Yannick Le Manach
Julije Mestrovic
Gabriele Finco
Publisher
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Careggi, Firenze, Italia
Università Vita-Salute San Raffaele,
Milano, Italia
Fortis Hospitals, Bangalore, India
WEB Site
Chiara Lazzeri
Yoshiro Hayashi
Kameda Medical Center, Kamogawa,
Chiba, Japan
The University of Queensland, Brisbane,
Australia
Luca Severi
Azienda Ospedaliera San Camillo
Forlanini, Roma, Italia
Andrea Szekely
Semmelweis University, Budapest, Hungary
Luigi Tritapepe
Università degli Studi “La Sapienza”,
Roma, Italia
James L. Januzzi
Emiliano Vitalini
Harvard University, Massachusetts
General Hospital, US
Ospedale San Camillo Forlanini, Roma,
Italia
CONTENTS
Q INVITED EDITORIAL
A comprehensive approach to refractory cardiac arrest:
saving more lives one way or another ................................................................................................................................................................... 149
I. Ortega-Deballon, E. De La Plaza-Horche
Q EXPERT OPINION
A simplified minimally invasive approach to mitral valve surgery optimal access under direct vision .............................................................................................................................................................................. 152
A. Amiri, E.M. Delmo Walter, R. Hetzer
Q REVIEW ARTICLE
Acute right heart syndrome in the critically ill patient
...................................................................................................
157
V. Zochios, N. Jones
Q ORIGINAL ARTICLE
Atrial fibrillation after isolated coronary surgery.
Incidence, long term effects and relation with operative technique
........................................................
171
.................................................................................
180
C. Rostagno, C. Blanzola, F. Pinelli, A. Rossi, E. Carone, P.L. Stefàno
Acute myocardial infarction associated to DPP-4 inhibitors
J.P.L. Nunes, J.D. Rodrigues, F. Melão
Agglutinins and cardiac surgery: a web based survey
of cardiac anaesthetic practice; questions raised and possible solutions
.....................................
187
S. Shah, H. Gilliland, G. Benson
Direct comparison between cerebral oximetry by INVOSTM
and EQUANOXTM during cardiac surgery: a pilot study ............................................................................................. 197
A. Pisano, N. Galdieri, T.P. Iovino, M. Angelone, A. Corcione
Q CASE REPORT
Life threatening tension pneumothorax during cardiac surgery.
A case report ........................................................................................................................................................................................................................................................... 204
A. Jain, D. Arora, R. Juneja, Y. Mehta, N. Trehan
Q IMAGES IN MEDICINE
Coronary to extra-cardiac anastomosis
............................................................................................................................................................
208
A. Mohsen, J. Loughran, S. Ikram
Internal thoracic vein: friend or foe?........................................................................................................................................................................ 210
A. Roubelakis, D. Karangelis, S.K. Ohri
Q FUTURE EVENTS ..........................................................................................................................................................................................................................................213
147
Invited Editorial
Heart, Lung and Vessels. 2014; 6(3): 149-151
A comprehensive approach
to refractory cardiac arrest:
saving more lives one way
or another
I. Ortega-Deballon1,2,3, E. De La Plaza-Horche3
1
McGill University Health Center, Montreal Children’s Hospital and Centre de Prélèvement
d’Organes, Hôpital du Sacré-Coeur de Montréal, Québec, Canada; 2Faculty of Medicine
and Health Sciences, University of Alcalá de Henares, Madrid, Spain; 3Helicopter and Ambulance
Emergency Medical Services SUMMA 112, Madrid, Spain
According with the last updated guidelines on resuscitation, the
underlying cause of cardiac arrest (CA) should be identified, treated and, if possible, reversed with different strategies but a common target: to increase long-term survival with good neurologic
recovery.
At the same time, some countries have implemented protocols for
donation after considering the irreversibility of cardiac arrest and
the failure of resuscitation attempts.
Both strategies are complementary and should coexist. Thus, we
would be able to go beyond the refractory CA firstly and, if not
indicated or unsuccessful, we could increase the organ donation
pool after confirming irreversibility.
International recommendations on resuscitation (1) highlight the
importance of high-quality cardiopulmonary resuscitation (CPR)
based on minimal interruptions, focused on determining the cause
of the cardiac arrest and offering, as early as possible, etiological
treatment of potential reversible causes. Several pioneering protocols have been developed throughout the world in order to provide
a multidisciplinary approach to the out-of-hospital (OHCA) and
in-hospital cardiac arrest (IHCA).
Moreover, international programs including non-conventional resuscitation procedures (NCRPs) have been set up (2-7).
Corresponding author:
Ivan Ortega-Deballon
Research Associate Critical Care Division
Montreal Children’s Hospital
2300, rue tupper. Montreal
Quebec. Canada. H3H 1P3
e-mail: [email protected]
Heart, Lung and Vessels. 2014, Vol. 6
149
I. Ortega-Deballon, et al.
150
Such an approach to refractory CA incudes:
1. High-quality CPR with minimal interruptions: ongoing CPR during transportation to the hospital through
automated chest compressors and ventilations, possible administration of
thrombolytics in pulmonary embolism
(1), and use of therapeutic mild hypothermia (3,7).
2. Management of IHCA, or incoming patient with OHCA undergoing CPR: percutaneous coronary intervention during CPR in coronary artery disease, or
ECLS followed by thrombolysis, placement of an intra-aortic balloon pump,
or therapeutic mild hypothermia (2-7).
The conclusions of published studies
highlight in the need of validating a predictive model, to establish teams trained
in the procedures, and to avoid delays in
the initiation of the ECLS technique after
admission of the patient to the hospital
(minimizing the so-called low-flow period) (2,4-7).
Some countries are a reference in programs for uncontrolled donation after circulatory death (uDCD) (9-12): a patient
who has an unexpected OHCA, and who
fails to CPR attempts is transferred with
continuing thoracic compressions and
ventilation with the sole aim of preserving the organs (12). Thus, is driven to a
hospital with the capacity to receive this
type of donor, rather than to the hospital
able to treat the underlying cause of CA,
when possible (9-12).
The family, if not at the scene are asked by
police to go to the hospital and there, they
receive notification of the death of their
relation. Transplant coordinators then
ask them for authorization to the organ
retrieval.
At this time, the deceased person is already in the operating room and has been
connected to an organ preserving system.
This type of uDCD program provides 10%
of all deceased donors in Spain (40% in
Madrid region) (12).
There are evident similarities between
the human, technical and logistical means
made available for NCRPs and those required by uDCD programs (9-11).
We, obviously, support the need to obtain
organs for donation, and the uDCD programs are essential for this laudable purpose (11).
However, priorities should be clear and
transparent: inclusion in the uDCD program should be considered only after benefiting patients of NCRPs, if they were eligible for it (9-11).
Moreover, recent protocols even show that
joining both strategies, not only survival
outcomes rate increases, but also graft
outcomes (3,7).
An unexplored path to achieve both these
goals might be to implement a comprehensive management of OHCA that includes
two options: ‘Non-conventional resuscitation procedures option’ in selected patients, focused on the reversible underlying primary cause of OHCA (option 1) or a
protocol for uDCD (option 2) if the ‘ongoing CPR option’ is not indicated or judged
futile, after conventional resuscitation attempts have been provided case-by-case.
To implement such a protocol requires to
build a bridge linking prehospital and hospital settings.
Thus, by trying to save hopeless patients’
lives, and when this is not possible, by increasing organ availability for transplantation, we will be providing excellent care
to patients suffering refractory cardiac
arrest on the field, and saving more lives
by one or other way: firstly, through highquality resuscitation, and secondly, when
really impossible even after the best attempts, retaining donation and transplantation options after declaring death.
Heart, Lung and Vessels. 2014, Vol. 6
A comprehensive approach to refractory cardiac arrest
REFERENCES
1. Nolan JP, Soar J, Zideman DA, Biarent D, Bossaert LL,
Deakin C, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summary. Resuscitation 2010; 81: 1219-76.
2. Sunde K. Experimental and clinical use of ongoing mechanical cardiopulmonary resuscitation during angiography and percutaneous coronary intervention. Crit Care
Med 2008; 36(11 Suppl): S405-8.
3. Fagnoul D, Taccone FS, Belhaj A, Rondelet B, Argacha JF,
Vincent JL, et al. Extracorporeal life support associated
with hypothermia and normoxemia in refractory cardiac
arrest. Resuscitation 2013; 84: 1519-24.
4. Chen YS, Lin JW, Yu HY, Ko WJ, Jerng JS, Chang WT,
et al. Cardiopulmonary resuscitation with assisted extracorporeal life support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac
arrest: an observational study and propensity analysis.
Lancet 2008; 372: 554-61.
5. Lazzeri C, Bernardo P, Sori A, Innocenti L, Stefano P,
Peris A, et al. Venous-arterial extracorporeal membrane
oxigenation for refractory cardiac arrest: a clinical challenge. Eur Heart J Acute Cardiovasc Care. 2013; 2: 118-26.
6. Adnet F, Baud F, Cariou A, Carli P, Combes A, Devictor
D, et al. Guidelines for indications for the use of extracorporeal life support in refractory cardiac arrest. French
7.
8.
9.
10.
11.
12.
Ministry of Health. Ann Fr Anesth Reanim 2009; 28:
182-90.
Belohlavek J, Kucera K, Jarkovsky J, Franek O, Pokorna
M, Danda J, et al. Hyperinvasive approach to out-of-hospital cardiac arrest using mechanical chest compression
device, prehospital intraarrest cooling, extracorporeal
life support and early invasive assessment compared to
standard of care. A randomized parallel groups comparative study proposal. “Prague OHCA study”. J Transl Med.
2012; 10: 163.
Dumas F, Cariou A, Manzo-Silberman S, Grimaldi D,
Vivien B, Rosencher J, et al. Immediate Percutaneous
Coronary Intervention Is Associated With Better Survival After Out-of-Hospital Cardiac Arrest. Insights From
the PROCAT (Parisian Region Out of Hospital Cardiac
Arrest) Registry. Circ Cardiovasc Interv 2010; 3: 200-7.
Doig CJ, Zygun DA. (Uncontrolled) donation after cardiac determination of death: a note of caution. J Law Med
Ethics 2008; 36: 760-5.
Bracco D, Noiseux N, Hemmerling TM. The thin line between life and death. Intensive Care Med 2007; 33: 751-4.
Rodríguez-Arias D, Ortega I. Protocols for Uncontrolled
donation after circulatory death. Lancet. 2012; 379: 12756.
Matesanz R, Coll Torres E, Dominguez-Gil Gonzalez B,
et al. [Donación en asistolia en España: situación actual y
recomendaciones]. ONT. 2012. Madrid.
Cite this article as: Ortega-Deballon I, De La Plaza-Horche E. A comprehensive approach to refractory cardiac arrest: saving
more lives one way or another. Heart, Lung and Vessels. 2014; 6(3): 149-151.
Source of Support: Nil. Disclosures: None declared.
Heart, Lung and Vessels. 2014, Vol. 6
151
EXPERT OPINION
Heart, Lung and Vessels. 2014; 6(3): 152-156
152
A simplified minimally invasive
approach to mitral valve surgery optimal access under direct vision
A. Amiri, E.M. Delmo Walter, R. Hetzer
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany
Heart, Lung and Vessels. 2014; 6(3): 152-156
ABSTRACT
With increasing enthusiasm in minimally invasive surgery, several approaches and access are being performed
with great precision. In this report, we illustrate and describe a minimal invasive approach to mitral valve surgery with optimal access under direct vision, the indications and patient selection, the surgical techniques, its
advantages over the other approaches, and its simplicity and reproducibility.
Keywords: mitral valve repair, minimally-invasive approach, anterolateral thoracotomy, cardiopulmonary bypass, myocardial protection.
INTRODUCTION
Over the past decade, minimally invasive
approaches to mitral valve surgery have
been commonly used at many centers
around the world with excellent short- and
long-term outcomes (1-5). There has been
great enthusiasm about their performance
because they have proven to be at least as
good and safe as the standard sternotomy
approach, even in elderly patients. A variety of approaches (6-8) have been reported,
aimed at reducing surgical trauma and postoperative morbidity while remaining safe
and effective. Some approaches have been
aided by the use of thoracoscopy, specially
designed retractors and surgical clamps as
Corresponding author:
Aref Amiri, MD
Deutsches Herzzentrum Berlin
Augustenburger Platz 1
13353 Berlin, Germany
e-mail: [email protected]
well as special instruments for long-distance knot-tying. The right thoracotomy
approach has been the most appealing, for
reasons of cosmesis and reduced trauma.
However minimally invasive mitral valve
surgery (MIMVS) is performed, the most
important consideration is that the approach must yield results equal to or better
than those of the approaches it modifies or
replaces. There has been increasing interest
in simplifying the operation so that it can
be widely applied to benefit patients.
This report illustrates a simplified, reproducible minimally invasive approach with
optimal access to and exposure of the mitral
valve (MV) under direct vision.
Patient selection
We applied this approach to all patients
with moderate and severe MV insufficiency
and/or stenosis of various etiologies, with
no concomitant coronary artery disease or
aortic valve regurgitation. Even complex re-
Heart, Lung and Vessels. 2014, Vol. 6
Optimal minimally invasive mitral valve surgery
pair procedures for severe bileaflet prolapse
in patients with Barlow’s disease can be successfully performed through this approach.
MV surgery using any commercially available prostheses can be performed with the
same reliability in patients in whom the
mitral valve is not amenable to repair. It is
also a useful alternative for patients requiring MV procedures after a previous cardiac
operation, particularly in those with patent
coronary artery bypasses or previous aortic valve replacement. This may also be applied in patients who had had surgeries via
right thoracotomy approach.
Assessment of mitral valve lesions
The degree of MV insufficiency or stenosis
is estimated by means of standard echocardiographic measurements. Assessment of
MV function includes measurement of the
mitral annulus, evaluation of leaflet mobility and coaptation, determination of mitral
valve orifice area, mitral flow assessment
using continuous wave Doppler, and valve
anatomy evaluation as to valve thickness
and pliability and morphology of the subvalvular apparatus.
Standard guideline in MIMVS using the
simplified approach
Because the mitral valve is a posterior
structure, excellent exposure can be established through the right anterolateral thoracotomy.
A simplified right anterolateral thoracotomy approach includes a 10-12 cm incision,
either direct aortic or peripheral arterial
cannulation and direct bicaval canulation,
with standard retractors.
Surgical technique
Under general anesthesia using a double
lumen endotracheal tube, the patient is
placed in left lateral position with the chest
elevated to about 45-60° (Figure 1A). The
right arm is placed over the head at approx-
153
Figure 1A - Position of the patient.
Figure 1B - Anterolateral thoracotomy incision
(10-12 cm) at the 5th intercostal space.
imately 120° with the elbow joint in the
right-angle position. The operating table is
rotated leftwards and the patient is bent at
the 12th thoracic vertebra. Transcutaneous
defibrillation pads (Philips Multifunction
Electrode Pads, Philips, Amsterdam, The
Netherlands) are placed at the left lateral
chest wall and right shoulder.
A 10-12 cm skin incision over the fifth anterolateral intercostal space is made beginning in the skin fold below the right breast
(Figure 1B).
The right lung is deflated and the chest cavity is entered without division or resection
of any bone. Standard chest retractors are
used and, under direct vision, the pericardium is incised parallel and approximately
3-4 cm anterior to the phrenic nerve. Several pericardial edge retention sutures are
placed anteriorly and posteriorly. This pro-
Heart, Lung and Vessels. 2014, Vol. 6
A. Amiri, et al.
Figure 1C - Optimal exposure
of intracardiac
structures with
aortic and bicaval cannulation
within the same
incision.
154
vides optimal and excellent visualization
and access to the ascending aorta and superior vena cava. Heparin is administered
and arterial cannulation is performed either directly in the ascending aorta or in
the common femoral artery (only in patients with a small and narrow chest) with
direct bicaval cannulation with caval snares
(Figure 1C). Adequate myocardial protection is achieved with intermittent blood
cardioplegia through a cardioplegia needle
in the aortic root. The ease and handling
of myocardial protection provides no difficulty and is comparable when the approach
is through a standard median sternotomy.
After clamping the ascending aorta with a
straight clamp having a flexible handle, the
left atrium is opened by incising the interatrial groove with a vent cardiotomy sucker
placed directly towards the left pulmonary
veins. A retractor is placed to elevate the interatrial septum, exposing the mitral valve,
and the valve is meticulously inspected to
determine the precise nature of the lesion.
Leaflet coaptation is assessed with transvalvular saline injection under pressure. Using a nerve hook, leaflet coaptation and the
presence of sufficient tissues along the coaptation plane are evaluated. Depending on
the results of this evaluation, mitral valve
repair or replacement is performed under
direct vision, using precisely the same approach as in a conventional median sternotomy.
Mitral valve repair
Modified Gerbode plication plasty (9) is
applied for posterior leaflet prolapse, ruptured chordae and in ischemic mitral insufficiency (MI).
Prolapse can occur anywhere along the posterior leaflet but is most commonly found in
the region of P2, which may lead to chordal
rupture. In this technique, the flail segment
is plicated towards the left ventricle in a Vshaped fashion with interrupted mattress
sutures using double-ended 3-0 polypropylene with untreated autologous pericardial
pledgets. Hence, the P1 segment is attached
to the P3 segment. When competence and
size are satisfactory a strip of untreated
autologous pericardium is sutured continuously onto the posterior annulus without
further annular narrowing.
Heart, Lung and Vessels. 2014, Vol. 6
Optimal minimally invasive mitral valve surgery
Modified Paneth-Hetzer posterior annulus shortening technique (9) is utilized for
severe annular dilatation and ischemic MI.
This is performed by running a pericardialpledgeted 3-0 polypropylene suture through
the fibrous body of the trigone and tying it.
Then it is run along the annulus from one
trigone towards the middle of the posterior
annulus. The same is done on the opposite
trigone.
These sutures are then tied over an appropriately sized Ziemer-Hetzer valve sizer to
prevent over-narrowing of the valve orifice. The valve is then tested with saline
injection for competence. Using the same
needles, both sutures are passed onto an
autologous pericardial strip. Then, with
a continuous suture, the pericardial strip
is attached to the posterior annulus from
the midsegment towards the trigone. The
leaflet coaptation is tested by a forceful injection of saline through the valve, to look
for residual regurgitation. We also use this
technique in anterior leaflet prolapse; the
then wider coaptation plane will eliminate
prolapse.
Evaluation of the adequacy of repair
After MV repair, it is obligatory to assess
the valve function before closure of the atrium and separation from cardiopulmonary
bypass (CPB). This is done by transvalvular
saline injection with a bulb syringe under
pressure. Any remaining areas contributing
to significant incompetence must be attended to before closure of the atrium.
Once de-airing has been completed and
extracorporeal circulation is discontinued,
the repair result must be further evaluated
with intraoperative transesophageal echocardiography (TEE) in order to test for
inadequate mitral opening area, residual
incompetence, myocardial ischemia due
to coronary kinking and presence of the
systolic anterior motion (SAM) phenomenon.
Immediate and prompt correction must be
made if the repair is shown to be unsatisfactory. Regardless of the underlying pathology and techniques used, no patient
should be discharged from the operating
room with more than minimal MI.
Mitral valve replacement
If it is established that the mitral valve lesion is not amenable to repair, the valve is
replaced, with either a mechanical or biological prosthesis, in accordance with the
patient’s wishes.
In both procedures, no specially designed
instruments are required, and the knots
may be tied by hand or with a knot pusher.
Several strategies of knot tying have been
learned with experience, such as having the
assistant hold up the annular sutures during knot tying.
After completion of the procedure, the left
ventricle is vented with a catheter positioned across the valve and the atriotomy
is closed.
Concomitant Maze procedure with radiofrequency ablation may also be performed,
when necessary. Caval snares are snugged
tight when tricuspid valve reconstruction
(double-orifice-valve technique) (10) or
closure of patent foramen ovale are performed, and these procedures are done
through right atriotomy.
Throughout the procedure, a vacuum-assisted venous drain in the heart-lung machine
is used and carbon dioxide is infused into
the operative field to decrease the chance
of air embolism. Complete evacuation of
intracardiac air is performed through the
aortic root and left atrium and confirmed
by TEE. Temporary atrial and ventricular
pacing wires are placed before releasing the
aortic clamp. Defibrillation, when necessary, is administered through the external
defibrillator pads.
Once the hemodynamic status is stable, cardiopulmonary bypass is discontinued and
Heart, Lung and Vessels. 2014, Vol. 6
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A. Amiri, et al.
156
decannulation is performed. Transesophageal echocardiography is mandatory at the
moment to document the repair results or
prosthetic function.
The right pleural space and mediastinum
are drained through the 7th intercostal
space with two chest tubes and the intercostal spaces are closed with five or six pericostal sutures.
associated with balloon malposition or migration (11).
This simplified approach combines good
cosmesis with optimal exposure of the mitral valve and all the cardiac structures, is
readily applicable and is not associated with
a steep learning curve because one employs
conventional cannulation and clamping
techniques.
REFERENCES
CONCLUSION
This simplified minimally invasive approach to mitral valve surgery with optimal
access to all cardiac structures and optimal
exposure of the mitral valve under direct
vision offers distinct advantages, including direct aortic root and caval cannulation
performed with ease and without obscuring the operative field, optimal exposure
and overview of the operative field, controlled myocardial protection, and adequate
de-airing.
Although the skin incision is 5-8 cm longer
than in the conventional minimally invasive technique, besides providing good cosmesis and an acceptable postoperative scar,
it outweighs the placement of additional
skin incisions for the other cannulae or
the aortic clamp, and obviously avoids the
potential complications related to femoral
vessel cannulation. Additionally, standard
aortic cross-clamping and antegrade cardioplegia delivery obviate the need for specialized endovascular occlusive balloons,
hence avoiding the potential complications
1. Davierwala PM, Seeburger J, Pfannmueller B, Garbade J,
Misfeld M, Borger MA, et al. Minimally invasive mitral
valve surgery: “The Leipzig experience”. Ann Cardiothorac Surg. 2013; 2: 744-50.
2. Galloway AC, Schwartz CF, Ribakove GH, Crooke GA,
Gogoladze G, Ursomanno P, et al. A decade of minimally
invasive mitral repair: long-term outcomes. Ann Thorac
Surg. 2009; 88: 1180-4.
3. Misfeld M, Borger M, Byrne JG, Chitwood WR, Cohn L,
Galloway A, et al. Cross-sectional survey on minimally invasive mitral valve surgery. Ann Cardiothorac Surg. 2013;
2: 733-8.
4. Cohn LH, Byrne JG. Minimally invasive mitral valve surgery: current status.Tex Heart Inst J. 2013; 40: 575-6.
5. Rittwick B, Chaudhuri K, Crouch G, Edwards JR,
Worthington M, Stuklis RG. Minimally invasive mitral
valve procedures: The current state. Minim Invasive Surg.
2013; 2013: 679276.
6. Angouras DC, Michler RE. An alternative surgical approach to facilitate minimally invasive mitral valve surgery. Ann Thorac Surg. 2002; 73: 673-4.
7. Tam RK, Ho C, Almeida AA. Minimally invasive mitral
valve surgery. J Thorac Cardiovasc Surg. 1998; 115: 246-7.
8. Modi P, Chitwood WR Jr. Retrograde femoral arterial perfusion and stroke risk during minimally invasive mitral
valve surgery: is there cause for concern? Ann Cardiothorac Surg. 2013; 2: E1.
9. Hetzer R, Delmo Walter EM. No ring at all in mitral valve
repair: indications, techniques and long-term outcome.
Eur J Cardiothorac Surg. 2014; 45: 341-51.
10. Hetzer R, Komoda T, Delmo Walter EM. How to do the
double orifice valve technique to treat tricuspid valve incompetence. Eur J Cardiothorac Surg. 2013; 43: 641-2.
11. Grocott HP, Smith MS, Glower DD, Clements FM. Endovascular aortic balloon clamp malposition during minimally invasive cardiac surgery: detection by trranscranial
Doppler monitoring. Anesthesiology. 1998; 88: 1396-9.
Cite this article as: Amiri A, Delmo Walter EM, Hetzer R. A simplified minimally invasive approach to mitral valve surgery optimal access under direct vision. Heart, Lung and Vessels. 2014; 6(3): 152-156.
Source of Support: Nil. Disclosures: None declared.
Acknowledgment: We thank Anne Gale for editorial assistance.
Heart, Lung and Vessels. 2014, Vol. 6
REVIEW ARTICLE
Heart, Lung and Vessels. 2014; 6(3): 157-170
Acute right heart syndrome
in the critically ill patient
V. Zochios, N. Jones
Cardiothoracic Intensive Care Unit, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, UK
Heart, Lung and Vessels. 2014; 6(3): 157-170
ABSTRACT
Acute right heart syndrome is a sudden deterioration in right ventricular performance, resulting in right ventricular failure and confers significant in-hospital morbidity and mortality. In critically ill patients, the syndrome is
often undiagnosed and untreated, as these patients do not usually exhibit the common clinical manifestations
of the condition, making the diagnosis challenging for the intensivist. In this narrative review we focus on the
pathophysiology of acute right heart syndrome, in critical illness, diagnostic modalities used to assess right ventricular function and management of acute right heart syndrome, including mechanical ventilation strategies
and circulatory support.
Keywords: critical illness, right heart failure, pulmonary artery pressure, mechanical ventilation, echocardiography.
INTRODUCTION
Acute right heart syndrome (ARHS) may
be defined as sudden deterioration in the
right ventricular (RV) function and failure
of the RV of the heart to deliver adequate
blood flow to the pulmonary circulation,
resulting in systemic hypoperfusion (1). In
the context of critical illness, ARHS is associated with poor outcomes and increased
mortality (2). Evidence of central venous
pressure (CVP) overload in conjunction
with RV contractile dysfunction, is usually
present in ARHS (1).
We searched PubMed, EMBASE, Cochrane
library and Google Scholar, for articles reCorresponding author:
Dr Vasileios Zochios
Cardiac Critical Care Fellow
Department of Cardiothoracic Anesthesia and Intensive Care
Cardiothoracic ICU
Papworth Hospital NHS Foundation Trust
Papworth Everard, Cambridge, UK, CB23 3RE
e-mail: [email protected]
porting on RV dysfunction and failure.
The relevant papers were extracted in full
and references from extracted papers were
checked for any additional relevant articles. An overview of the ARHS pathophysiology, diagnostic tools for the assessment
of the acutely failing RV in critical illness
and measures including vasoactive agents,
ventilatory strategies and mechanical support is provided in the current paper.
THE RV IN HEALTH
The main functions of the RV are:
a) maintenance of adequate pulmonary
perfusion pressure in order to deliver
desaturated mixed venous blood to the
respiratory membrane;
b) maintenance of low systemic venous
pressure in order to prevent organ congestion.
Heart, Lung and Vessels. 2014, Vol. 6
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V. Zochios, et al.
158
The RV is anatomically adapted for the
generation of low-pressure perfusion and
it is very sensitive to changes in afterload.
(3). The differences between the structure
and function of the RV compared to the left
ventricle (LV) are outlined in Table 1 and
Figure 1 compares the pressure-volume (PV) loop of the RV with that of the LV (3-5).
THE RV IN CRITICAL ILLNESS
ARHS is not necessarily associated with
an increase in pulmonary vascular resistance (PVR) and pulmonary arterial hypertension (PAH) (6). The syndrome can
be due to RV pressure/volume overload
or RV contractile dysfunction (1). Consequence is low cardiac output (CO) with low
mean arterial pressure (MAP), exacerbating RV dysfunction.
Thus, “RV failure begets RV failure” leading to a progressive downward spiral of
worsening ischemia, myocardial dysfunction and shock. In mechanically ventilated
patients with ARHS, low CO is multifacto-
rial and could be due to RV systolic dysfunction, tricuspid regurgitation, ventricular interdependence (dilatation of the RV
shifting the interventricular septum toward the left and decreasing the LV distensibility and preload), arrhythmias or suboptimal preload (6). RV diastolic dysfunction causes impaired RV filling and high
diastolic RV and right atrial (RA) pressures leading to organ congestion (6). The
causes and precipitating events of ARHS
are summarized in Table 2 (7-15).
ARHS in Acute Respiratory Distress
Syndrome (ARDS)
ARDS is one of the most common causes
of ARHS secondary to RV pressure overload (acute cor pulmonale). In critically ill
ventilated patients with ARDS, ARHS occurs in 61% of patients submitted to conventional tidal volume mechanical ventilation (MV) and 25% of those receiving lung
protective MV using low tidal volumes (15,
16). Apart from MV, the pathologic features of the syndrome per se, contribute to
increased pulmonary vascular tone, acute
Table 1 - Differences between RV and LV (3-9, 25).
Structure
Shape
in cross
section
Enddiastolic
wall
thickness
Enddiastolic
volume
Systolic
Pressure
Ejection
fraction
Coronary
perfusion
Response
to disease
Pressurevolume loop
RV
Inflow region,
infundibulum
Semicircular
/serpentine
shape
≤3 mm
49-101
ml/m2
25 mmHg
40-68%
Continuous
(systole &
diastole)
Better
adaptation
to volume
overload
states,
higher
compliance
than LV
Trapezoidal
with poorly
defined
isovolumetric
periods - RV
pressure rise
and ejection
continue
despite fall in
RV pressure.
LV
No
infundibulum
mitro-aortic
continuity
Circular
≤11 mm
44-89 ml/m2
120 mmHg
57-74%
Almost
exclusively
in diastole
Better
adaptation
to pressure
overload
states
Rectangular
- rapid rise
and fall of
pressure with
ejection
RV = right ventricle; LV = left ventricle.
Heart, Lung and Vessels. 2014, Vol. 6
Acute right heart syndrome in critical illness
159
Figure 1 - Pressure-volume (P-V) loops for RV and LV. Once RV pressure reaches the PA pressure, the
pulmonary valve opens. Little time is spent in isovolumetric contraction, giving a triangular-shaped RV
P-V loop, in contrast to the almost square loop of the LV (25). (Adopted from: Kevin LG, Barnard M.
Right ventricular failure. Contin Educ Anaesth Crit Care Pain 2007; 7: 89-94). Permission to reproduce
granted under Oxford university press’s general terms.
RV = right ventricle; LV = left ventricle.
Table 2 - Precipitating events / causes of ARHS in the ICU (7-15).
RV pressure overload (endothelial dysfunction, vasoconstriction, mechanical obstruction)
1. Massive pulmonary embolism.
2. Acute Respiratory Distress Syndrome.
3. Deteriorating chronic pulmonary arterial hypertension.
4. Post cardiothoracic surgery
5. Mechanical ventilation.
6. Pulmonary valve stenosis.
7. Hypoventilation state
RV volume overload
1. Pulmonary or triscupid valve regurgitation.
2. Left to right shunt due to inter-atrial defect.
3. Anomalous pulmonary venous return.
4. Hyperthyroidsm
RV contractile dysfunction
1. RV myocardial infarction (via negative inotropic effect or arrhythmia).
2. Relative RV ischemia secondary to RV pressure or volume overload.
3. Intrinsic myocardial disease e.g RV cardiomyopathy, sepsis (cytokine induced myocardial
depression), inflammatory effects of cardiopulmonary bypass, myocarditis.
4. Pericardial disease e.g constrictive pericarditis, tamponade (causing impaired diastolic filling).
5. Left ventricular assist device (due to acute unloading of the LV).
LV dysfunction (by increasing pulmonary venous and pulmonary arterial pressure, myocardial
ischemia, LV dilatation leading to restricted RV diastolic function).
ARHS = acute right heart syndrome; ICU = intensive care unit; RV = right ventricular; LV = left ventricular.
Heart, Lung and Vessels. 2014, Vol. 6
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160
pulmonary arterial hypertension (PAH)
and cor pulmonale. Contributors to elevated pulmonary vascular resistance (PVR)
in ARDS include: vasoconstrictor: vasodilator imbalance (excess ET-1, 5HT, PDE,
reduced NO and prostanoids), endothelial
injury, hypoxic pulmonary vasoconstriction (80% arteriolar), hypercapnia (including permissive hypercapnia), acidemia, in
situ thrombosis and pulmonary vascular
remodelling (muscularization of non-muscularized arteries) (8, 16, 17).
tered vaso-reactivity, despite concomitant
decrease in systemic vascular resistance
(SVR). Substantial increases in PVR also
occur when the left ventricle needs to considerably increase the cardiac output in order to compensate for the fall in the SVR,
causing further increase in RV afterload
(21, 22).
ARHS in the setting of massive
pulmonary embolism (PE)
Critically ill patients are at risk of PE despite thromboprophylaxis (3, 18). In a tenyear retrospective study, Vieillard-Baron et
al. (19) showed that ARHS was present in
61% of medical intensive care unit (ICU)
patients with massive PE and carried a
23% mortality.
The normal RV can generate a mean pulmonary artery pressure up to 40 mmHg,
requiring 50-75% of the pulmonary vasculature to be occluded by emboli before
acute RV failure occurs (19).
Hypoxemia induced by the emboli results
in pulmonary vasoconstriction and the
physiological response to platelet activation
leading to release of vasoactive agents such
as serotonin, thromboxane and histamine,
causes further increase in PVR and RV
pressure overload (19, 20).
CLINICAL FEATURES
The clinical features of ARHS, including
acute onset shortness of breath, orthopnea
and bilateral lower extremity edema, are
non-specific and difficult to identify in the
sedated critically ill patient (6). Increased
oxygen requirements or sudden cardiovascular collapse might be the chief clinical
manifestations of ARHS in a mechanically
ventilated patient (23).
Other prominent clinical signs include
atrial or ventricular arrhythmias, raised
jugular venous pressure and gallop rhythm
at the left sternal edge, systolic murmur
of tricuspid regurgitation, organomegaly,
signs of deep venous thrombosis (in the
context of venous thromboembolism) (6).
It is important to consider ARHS in persistent respiratory weaning failure (RV
dysfunction leads to an imbalance between
ventilator needs and cardiorespiratory capacity), especially in patients with LV systolic dysfunction (6, 9, 24, 25). A high index
of suspicion is needed in high risk patients
such as those with pre-existing PAH and
recent deep venous thrombosis (25).
ARHS in sepsis
In severe sepsis and septic shock the RV
function might be impaired. RV systolic
dysfunction in sepsis is directly associated
with markers of endothelial dysfunction
(endothelin 1, vascular cellular adhesion
molecule 1) and directly related to the severity of sepsis (21).
A proposed mechanism for ARHS in sepsis is increased PVR secondary to sepsisinduced endothelial cell injury and al-
DIAGNOSIS OF ARHS
IN THE CRITICALLY ILL
BEDSIDE STUDIES
Available bedside studies include: chest
X-ray (CXR), electrocardiography (EKG),
arterial blood gas (ABG) analysis, hemodynamic and echocardiographic diagnostic
tools.
Heart, Lung and Vessels. 2014, Vol. 6
Acute right heart syndrome in critical illness
Chest X-ray
Enlargement of the main pulmonary artery and regional oligemia are seen in massive PE. However, CXR cannot be utilized
to confirm the diagnosis of ARHS and
should only contribute to the diagnostic
approach by ruling out conditions that
mimic ARHS in the ICU, such as atelectasis, pleural effusions, pulmonary edema
and pneumothorax (6).
Electrocardiography
Kucher et al. showed that Qr in V1 is a
strong predictor of RV dysfunction, and
it is highly associated with troponin leakage and myocardial shear stress (26). It has
also been demonstrated that in patients
with right bundle branch block, R duration
in lead V1>100 ms is predictive of RV systolic dysfunction (43).
Other EKG findings suggestive of RV strain
include inversion of T waves in leads V1V4 and the classic S1Q3T3 pattern. Acute
anterior Q-wave pattern in leads V1-V3,
as well as a right-sided Q pattern in leads
V3R–V6R, might suggest RV infarction (12).
EKG, although specific, lacks sensitivity
(11).
Arterial blood gas analysis
ABG analysis may reveal grossly impaired
gas exchange and low cardiac output might
result in acidemia with lactic acidosis due
to tissue hypoperfusion (27).
Hemodynamic bedside diagnostic modalities
Central venous catheters and central
venous pressure
An accurately placed central venous catheter (in the superior vena cava), can provide
information on CVP and used as a surrogate for RV end-diastolic volume (RVEDV)
and RV end-diastolic pressure (RVEDP)
(25, 28). In severe tricuspid regurgitation
causing ARHS, a broad, tall systolic c-v
wave is seen due to abnormal systolic fill-
ing of the right atrium (RA) and the CVP
trace is said to be ventricularized because
it resembles right ventricular pressure (25,
28). RVEDP reflects RVEDV (which is proportional to preload) only when ventricular compliance is normal.
Therefore, in conditions such as PAH, tamponade and myocardial ischemia, where
RV compliance is decreased, CVP is likely
to be raised and cannot be accurately assessed (28, 29).
Right heart catheterization
Right heart catheterization using a pulmonary artery catheter (PAC) is frequently required when ARHS is clinically suspected
and interpretation of imaging studies is
difficult or inconclusive. Hemodynamic
data obtained from an accurately placed
PAC, by thermodilution, may provide diagnostic clues and guide therapy. PAC allows
direct simultaneous measurement of RA,
RV, PA and pulmonary artery wedge pressures and indirect measurement of cardiac
output, cardiac index (CI), RV stroke work
index, mixed venous oxygen saturation,
PVR and SVR (29, 30).
Hemodynamically, ARHS is suspected if
RA pressure >8-10 mmHg, or RA pressure to pulmonary capillary wedge pressure ≥0.8 (isolated RV failure) and CI is
low. In the presence of RV-PA gradient
>25 mmHg, RV outflow tract obstruction
should be excluded by echocardiography
(31).
In the context of PAH and suspected
ARHS, right heart catheterization allows
assessment of left-sided heart disease and
its contribution to PAH. Besides, calculation of PVR and SVR help decide whether
pulmonary or systemic vasodilators/pressors are needed and monitor response to
therapy (29). In patients with pre-existing
PAH, a decrease in PA pressure might reflect low RV ejection fraction and worsening RV dysfunction (12).
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V. Zochios, et al.
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Arterial pulse contour analysis
Arterial pulse contour analysis enables
calculation of CO, pulse pressure variation (PPV), stroke volume variation (SVV)
and SVR, from the arterial pulse pressure
waveform, in mechanically ventilated patients. Dynamic indices (SVV, PPV) have
been used to predict preload responsiveness and monitor the hemodynamic effect
of volume expansion in critically ill patients (32).
Wyler Von Ballmoos et al. reported that
PPV is not accurate predictor of fluid responsiveness in mechanically ventilated
patients with acute PAH (at risk of ARHS),
early after cardiac surgery and in septic
shock (33). In the context of a pressure
overloaded RV, increased PPV values are
related to an increase in the RV afterload
and not to a decrease in RV preload and
therefore, further volume expansion could
potentially be harmful (33, 34). However,
it could be reasonably contended that lack
of response to a fluid challenge, while PPV
or SVV is high, could be seen as an indicator of RV dysfunction necessitating further
investigations (35).
Bedside imaging modalities
Echocardiography
Transthoracic (TTE) and transesophageal echocardiography (TEE) are bedside
diagnostic tools which also provide rapid
risk stratification and could potentially direct therapeutic strategies. In experienced
hands, echocardiography allows assessment of the RV performance and loading conditions. Useful echocardiographyderived measures of RV function, when
ARHS is clinically suspected are outlined
in Table 3 (36).
TTE is an easy and non-invasive way to assess the size and kinetics of the RV. The
diagnosis of ARHS due to RV pressure
overload, with TTE, has good positive predictive value for indirect diagnosis of massive PE (37). Main limitations of TTE in
critically ill patients ventilated with high
level of positive end-expiratory pressure
(PEEP) include: inadequate imaging due to
interposition of the inflated lung between
the heart and the chest wall, low diagnostic
accuracy in the patients with pre-existing
cardiopulmonary disease, the operator dependent nature of TTE (37).
Table 3 - Echocardiographic quantitative parameters pointing towards ARHS (36-38).
RV systolic dysfunction
1. TAPSE <16 mm
2. 2D RV FAC < 35%
3. RIMP >0.4 by pulsed Doppler and >0.55 by tissue Doppler
RV diastolic dysfunction
1. E/A <0.8 by tissue Doppler
2. E/A >2.1 by tissue Doppler
Dilated RV chamber
1. Diameter >32 mm at the base
2. Diameter >35 mm at the mid-level
3. Longitudinal dimension >86 mm
RVOT dilatation
1. Diameter >27 mm at end-diastole at the level of pulmonary valve
RV = right ventricular; TAPSE = tricuspid annular plane systolic excursion; 2DRVFAC = two-dimensional right ventricular fractional area change; RIMP = right ventricular index of myocardial performance; E/A = early (E) to late (A)
ventricular filling velocities ratio; RVOT = right ventricular outflow tract .
Heart, Lung and Vessels. 2014, Vol. 6
Acute right heart syndrome in critical illness
RV function, size and shape, are more accurately assessed with TEE.
It has been suggested that in the presence
of significant and otherwise unexplained
RV strain without clots present on TTE,
TEE should rapidly follow at the bedside,
providing there is local availability and
expertise (38). TEE is a semi-invasive procedure and commonly reported complications associated with TEE in critically ill
patients receiving MV, include: hypo- or
hypertension, dysrrhythmias, trauma to
the gastrointestinal tract, hypoxemia and
dislodgment of endotracheal or nasogastric
tubes. The over-all complication rate associated with TEE use is low and it is estimated to be approximately 2.6% (38).
Additional imaging modalities
Computed tomography (CT)
CT pulmonary angiography (CTPA) is being used increasingly as a diagnostic tool
in PE, with documented sensitivities of
50-100% and specificities of 81-100% (39).
CTPA has become the preferred diagnostic
modality for suspected ARHS due to PE,
in hemodynamically stable ICU patients
(66). Chest CT signs suggestive of ARHS
include: flattening or displacement of the
intraventricular septum toward the LV,
reflux of contrast into the inferior vena
cava, RV diameter (RVD) to LV diameter
(LVD) ratio on axial sections greater than
1.0 (RVDaxial/LVDaxial >1) (39).
Cardiovascular Magnetic Resonance
(CMR)
CMR is the most sensitive method to assess
the RV size and function. Imaging quality
is not influenced by acoustic windows or
pre-existing cardiopulmonary disease (40).
However, CMR is rarely used for ICU patients receiving MV, as the MR environment carries significant risks to patients
during transportation and prolonged periods in the MR scanner.
LABORATORY TESTS
The usefulness of laboratory tests such as
D-dimmer, troponins and B-type natriuretic peptide levels, as diagnostic tests in
ICU patients with suspected RV failure, is
limited, as they are non-specific and confounded in the context of critical illness
(41, 42).
In summary, in critically ill patients with
clinically suspected ARHS, echocardiography (TTE and/or TEE) and right heart
catheterization are the preferred diagnostic modalities. If PE is the most likely cause
of ARHS, then CTPA is necessary to confirm the diagnosis, provided the patient is
suitable for transfer to radiology.
In any given scenario, the diagnostic approach will depend upon the expertise and
availability of the different diagnostic modalities.
TREATMENT
The principles and key components of
ARHS management include reversal of
precipitating events and control of contributing factors (hypoxemia, hypercapnia,
anemia, acidemia, sepsis, dysrrhythmias),
fluid volume optimization, maintenance of
perfusion pressure, positive inotropy, use
of pulmonary vasodilators and protective
MV (12, 43). The management principles
and strategies will depend upon the primary hemodynamic pathology.
Control of contributing factors, general
ICU care and reversible causes of ARHS
Infection prevention, treatment of sepsis
in accordance with the surviving sepsis
campaign bundles, normoxia, normocapnia, thromboprophylaxis, peptic ulcer prophylaxis, correction of acid-base imbalance
and electrolytes and glycemic control are
mandatory and applied to most ICU patients (12). Pulmonary vasodilators and/
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V. Zochios, et al.
164
or inodilators (in acutely decompensated
PAH), thrombolysis (in massive PE), revascularization (in RV infarction) and sequential AV pacing and/or cardioversion (in significant dysrrhythmias), could potentially
correct the abnormal RV physiology (44).
Optimization of intravascular fluid
status
Fluid loading in ARHS remains controversial. RV ejection fraction is dependent on
RV pre-load, in the abscence of PAH and it
is likely that RV output will be inadequate
in hypovolemia. The RV can increase the
stroke work through an increase in RV free
wall stretch (via the Frank-Starling mechanism) (29). Therefore, optimization of preload may improve RV ejection fraction.
The role of CVP as a guide to fluid therapy
remains controversial. A systematic review
of 24 studies demonstrated a poor relationship between CVP and intravascular fluid
status and the inability of CVP/delta-CVP
to predict the hemodynamic response to a
fluid challenge (32, 45).
Depending on where the patient is on the
Frank-Starling curve, some may be adequately resuscitated with a CVP of 6-7 mm
Hg, while others may still be intravascularly volume depleted at a CVP of 10 mm
Hg (31). In a recent meta-analysis, Marik
et al. showed that there is paucity of data
to support the widespread practice of using CVP to assess intravascular fluid status and guide fluid therapy (46). More reliable hemodynamic assessment tools, such
as PAC, pulse contour analysis, TTE and/
or TEE when available, may be utilized to
guide fluid therapy in ARHS (32).
Mercat et al. showed that in critically ill
medical patients with circulatory failure
(defined by CI <2.5 L/min/m2), due to
massive PE, fluid loading with 500 ml of
colloid increased the cardiac index significantly and improved hemodynamic status
(47). If the hemodynamic response to ini-
tial fluid challenge is poor, in the context of
ARHS, further volume loading may cause
RV overdistension, increased ventricular
interdependence, decreased LV filling and
RV ischemia, leading to worsening shock
(44). In RV volume overload, acute kidney
injury due to venous congestion (cardiorenal syndrome), continuous veno-venous
hemofiltration (CVVH) facilitates greater
clinical improvement compared with aggressive diuretic therapy, in heart failure
patients, who are diuretic resistant (48).
The role of vasopressors in ARHS
In order to preserve adequate right coronary blood flow, systemic pressure should
be maintained above the PA pressures.
It has been shown that in patients with
sepsis, PAH and RV dysfunction, norepinephrine increases systemic pressure
through alpha-1 receptor agonism and may
improve the RV oxygen supply/demand
ratio, but this potentially beneficial effect
on RV ejection fraction may be offset by a
concomitant increase in PVR and RV afterload, at high doses (>0.5 mcg/kg/min)
(43, 49). Besides, norepinephrine, through
beta-1 receptor agonism could potentially
improve RV-PA coupling and CO (22). Low
dose vasopressin (0.033-0.067 U/min) mediates pulmonary arterial vasodilation and
may be useful in vasodilatory shock and
pulmonary vascular dysfunction, especially in norepinephrine resistant patients (43,
49, 50).
Inotropes and inodilators in ARHS
Dobutamine (beta-1 receptor agonist) can
be used as the first-line inotropic agent in
ARHS due to RV contractile dysfunction.
Low dose dobutamine (2-5 mcg/kg/min)
increases CI, SV and decreases PVR and
SVR (12, 43, 51). At higher doses (>10 mcg/
kg/min) dobutamine causes tachycardia,
increased oxygen consumption, increased
PVR and leads to systemic hypotension
Heart, Lung and Vessels. 2014, Vol. 6
Acute right heart syndrome in critical illness
and addition of a vasopressor might be
required (12, 51). High quality evidence
suggests that dopamine is associated with
increased tachyarrhythmias and is not recommended in cardiogenic shock (45). It has
been demonstrated that in patients with
septic shock and ARHS, who are unresponsive to fluid loading, dopamine or dobutamine, epinephrine improves RV contractility in spite of a rise in mean PAP by
11% (p<0.05) (52). Selective phosphodiresterase (PDE) III inhibitors (enoximone,
milrinone, amrinone), augment myocardial contractility and cause systemic and
pulmonary vasodilaton, by increasing cyclic adenosine monophosphate (cAMP) and
thus reducing PA pressures and improving
RV function in patients with ARHS due
to pressure overloaded RV (43). Systemic
hypotension should be expected and addition of a vasopressor might be needed. It
has been demonstrated that levosimendan,
a calcium sensitizer with pulmonary vasodilator properties (inodilator), improves
RV performance in ARHS secondary to
sepsis-induced ARDS and in experimental
ARHS restores RV-PA coupling better than
dobutamine (53). In ARHS, levosimendan
has been shown to reduce the increased RV
afterload and ventricular interdependence,
improve RV contractility and RV diastolic
function, without significant increase in
oxygen consumption, mediated by opening
of sarcolemmal and mitochondrial potassium-adenosine triphosphate channels (54,
55). Although levosimendan is indicated
for the treatment of acute heart failure
(class of recommendation IIa, level of evidence B), it is has not yet been approved in
all countries (54, 55).
Pulmonary vasodilation in ARHS
The goals of pulmonary vasodilation in
ARHS are:
1) decrease PVR and impedance;
2) increase RV stroke volume and output;
3) avoid systemic hypotension and maintain coronary perfusion;
4) avoid hypoxemia from ventilation-perfusion mismatch.
It is recommended that inhaled nitric oxide (NO), which increases intra-cellular
cyclic guanosine monophosphate (cGMP),
should be considered as short term therapy
to improve PaO2/FiO2 ratio and CO, in ventilated patients with ARHS secondary to
ARDS (43). It has also been suggested that
NO may be effective in stabilizing patients
with ARHS due to massive PE until more
definitive treatment is available (29, 56).
Prostanoid formulations (epoprostenol, iloprost) are potent pulmonary and systemic
vasodilators with anti-thrombotic and anti-proliferative actions. They reduce PVR
and improve RV function and they have
been used in ARHS due to RV pressure
overload (57).
It has been shown that use of intravenous
epoprostenol in mechanically ventilated
patients with ARDS reduces PVR and improves RV performance (58).
Sildenafil, a PDE 5 inhibitor, increases
downstream cGMP signaling and potentiates the beneficial effects of NO. It reduces
PVR and increases CO and myocardial
perfusion (29). Karakitsos et al. showed
that mechanically ventilated patients with
ARHS from PAH, who were dependent on
dobutamine, were treated with oral sildenafil and in many cases they were successfully weaned from inotropic and ventilatory support (59).
Mechanical ventilation strategies
in ARHS
Optimal MV ventilation management in
ARHS consists of: avoidance of hypoxemia, hypercapnia, high levels of PEEP
(>10 cmH2O) and both high and low extremes of lung volumes and use lung protective ventilation strategies if possible (43,
60-62).
Heart, Lung and Vessels. 2014, Vol. 6
165
V. Zochios, et al.
166
The RV afterload is governed by PVR
which is directly affected by changes in
lung volume (61). Increased PVR occurs
at both low and high lung volumes. At low
volumes this is due to the elastic recoil
forces of the lung parenchyma leading to
extra-alveolar vessel collapse and terminal
airway collapse leading to alveolar hypoxia
and hypoxic pulmonary vasoconstriction
(HPV) and at high lung volumes due to
collapse of the alveolar vessels via stretch
of the alveolar wall. When PVR is plotted
against lung volume, a typical U-shaped
curve occurs with the lowest PVR occurring at functional residual capacity (FRC)
(Figure 2) (62). Schmitt et al. assessed the
impact of PEEP on the RV outflow impedance using doppler data obtained by TEE,
in mechanically ventilated ICU patients
with ARDS. They demonstrated that high
PEEP (13±4 cmH2O) was associated with
increased RV afterload and worsening RV
systolic dysfunction (60).
The significant decrease in the incidence of
ARHS (from 61% to 25%) in ARDS since
ARDSnet trial was published, reflects a
change in MV practice and suggests that
lung protective strategies (tidal volume: 6-8
ml/kg predicted body weight (PBW), low
plateau pressures and PEEP) reduce the incidence of ARHS (63).
In patients with ARHS, during lung protective ventilation, permissive hypercapnia should be avoided as acute hypercapnia
could lead to pulmonary vasoconstriction
or exacerbate hypoxic pulmonary vasoconstriction and could potentially worsen RV
dysfunction (64). A prospective observational study, which evaluated the relative
roles of acute permissive hypercapnia and
PEEP variations on RV function, in severe
ARDS patients, showed that increasing
PEEP at constant Pplat induces acute hypercapnia that may impair RV function and
decrease CI. It is therefore recommended
that in cases of ARHS, lung protective
ventilation should be gradually adapted to
limit hypercapnia and RV overload (65).
In mechanically ventilated ICU patients
with ARHS, refractory hypoxemia and/
or hypercapnia and high PEEP requirements, extracorporeal membrane oxygenFigure 2 - Effect of changing
lung volume on pulmonary
vascular resistance (PVR)
(62). (Adopted from: Shekerdemian L, Bohn D. Cardiovascular effects of mechanical
ventilation. Arch Dis Child
1999; 80: 475-480). Permission to reproduce granted under BMJ Publishing Group
Ltd’s general terms.
RV = residual volume; FRC
= functional residual capacity; TLC = total lung capacity.
Heart, Lung and Vessels. 2014, Vol. 6
Acute right heart syndrome in critical illness
ation (ECMO) could be used as a bridge
to the recovery of respiratory function.
Oxygenation and carbon dioxide clearance
are provided by the extracorporeal circuit,
minimizing pulmonary vasoconstriction
due to hypoxemia and/or hypercapnia (66,
67). In patients with ARHS due to severe
ARDS, where lung protective ventilation
may not be adequate in managing hypercapnic acidosis, extracorporeal carbon dioxide (ECCO2) removal devices are an option, as they are less invasive than ECMO
and may play a role in instituting “ultraprotective” lung ventilation (tidal volume:
4 ml/kg PBW) (68).
It should be noted that the cardiac consequences of weaning from MV may be responsible for weaning failure in patients
with ARHS. In these patients, an increase
in weaning-induced RV afterload may occur due to marked increase in work of
breathing, hypoxemia or high intrinsic
PEEP, leading to further worsening RV enlargement during weaning. This may result
in leftward shift of the interventricular
septum, impeding LV diastolic filling and
LV output (ventricular interdependence),
causing pulmonary edema and failure to
wean from MV (69).
shock, after systemic thrombolysis. It can
be used as a means of unloading the RV and
supporting systemic circulation, in medically refractory RV failure with accompanying hypotension and end-organ failure
and as a bridge to transplant (74, 75).
Right ventricular assist devices (RVADs)
in ARHS may be used as a bridge to recovery or transplant, or as a definitive surgical
treatment, in primary RV dysfunction. In
patients who are successfully weaned from
the RVAD, residual RV dysfunction is
compatible with survival (76). It has been
suggested that RVADs should be avoided
in patients with ARHS secondary to RV
afterload resistance (with severely elevated
PVR), as pumping blood into the PA could
potentially cause worsening PAH and lung
injury, whereas CO and CI remain low. In
such cases VA ECMO might be more effective in off-loading the RV (77).
The use of mechanical cardiovascular support devices depends largely on local availability of specialized facilities, cardiopulmonary pathophysiology expertise and operator experience.
Mechanical circulatory support
Low cardiac output syndrome caused by
ARHS after cardiac surgery, particularly
coronary artery bypass graft surgery and
heart transplant, may be an indication for
intra-aortic balloon pump (IABP) (70, 71).
It has been demonstrated that IABP improves hemodynamics and RV efficiency in
acute ischemic RV failure (72). However, a
recent RCT failed to demonstrate any mortality benefit in patients with cardiogenic
shock complicating acute myocardial infarction (73).
Veno-arterial (VA) ECMO has been used
as a salvage therapy in cases of ARHS due
to massive PE and refractory cardiogenic
ARHS can occur in many critical illnesses
and carries substantial morbidity and mortality. ARHS is difficult to diagnose in the
critically ill as those patients have ongoing
physiological derangement presenting the
intensive care specialists with a diagnostic dilemma. Cardiac echo and right heart
catheterization are invaluable diagnostic
tools in the assessment of the RV at the
bedside, which also provide a rapid risk
stratification and could direct treatment
strategies.
Characterizing, identifying and correcting
reversible factors is of paramount importance. Minimizing RV afterload (pulmonary vasodilators, inodilators, RV “protec-
CONCLUSION
Heart, Lung and Vessels. 2014, Vol. 6
167
V. Zochios, et al.
168
tive” MV strategies) and maximizing RV
performance (preload, inotropy, mechanical circulatory support) are the major components of ARHS management. Need for
mechanical circulatory support, merits referral to specialized treatment centres, if
there is insufficient local expertise or capacity. There is lack of definitive data regarding the management of ARHS in ICU
patients, without pre-existing cardiopulmonary disease.
Therefore, some recommendations may
rely on lower level of evidence or expert
opinion. Well-designed and adequately
powered RCTs are required to estimate
the prevalence of ARHS among critically
patients receiving MV, improve the understanding of its mechanisms in the context
of critical illness and evaluate the efficacy
of therapy guided by invasive and non-invasive hemodynamic monitoring tools.
REFERENCES
1. Greyson CR. Pathophysiology of right ventricular failure.
Crit Care Med 2008; 36: S57-65.
2. Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H,
Jorfeldt L. Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. Am Heart J 1997; 134: 479-487.
3. Bleeker GB, Steendijk P, Holman ER, Yu CM, Breithardt
OA, Kaandorp TA, et al. Assessing right ventricular function: the role of echocardiography and complementary
technologies. Heart 2006; 92: 19-26.
4. Alaverdian A, Cohen R. The Right Ventricle in critical illness.
The Open Critical Care Medicine Journal 2010; 3: 38-42.
5. Kevin LG, Barnard M. Right ventricular failure. Contin
Educ Anaesth Crit Care Pain 2007; 7: 89-94.
6. Zochios V, Keeshan A. Pulmonary embolism in the mechanically-ventilated critically ill patient: is it different?
JICS 2013;14:36-44.
7. Reis Miranda D, Gommers D, Lachman B. Effect of mechanical ventilation on right ventricular afterload. In:
Gullo A, eds. Anaesthesia, Intensive Care and Emergency
Medicine. Trieste: Springer, 2006; 361-366.
8. Cecconi M, Johnston E, Rhodes A. What role does the right
side of the heart play in circulation? Crit Care 2006; 10
(Suppl. 3): 6.
9. Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right
ventricular function in cardiovascular disease. I. Anatomy,
physiology, aging, and functional assessment of the right
ventricle. Circulation 2008; 117: 1436-48.
10. Forrest P. Anaesthesia and right ventricular failure. Anaesth Intensive Care 2009; 37: 370-85.
11. Giovambattista R D. Hyperthyroidism as a reversible cause
of right ventricular overload and congestive heart failure.
Cardiovasc Ultrasound 2008; 6: 29.
12. Lahm T1, McCaslin CA, Wozniak TC, Ghumman W, Fadl
YY, Obeidat OS, et al. Medical and surgical treatment of
acute right ventricular failure. J Am Coll Cardiol. 2010; 56:
1435-46.
13. Santambrogio L, Bianchi T, Fuardo M, Gazzoli F, Veronesi R, Braschi A, et al. Right ventricular failure after
left ventricular assist device insertion: preoperative risk
factors. Interact Cardiovasc Thorac Surg. 2006; 5: 37982.
14. Michael R, Pinsky M . Recent advances in the clinical application of heart- lung interactions. Curr Opin Crit Care
2002; 8: 26-31.
15. Jardin F, Gueret P, Dubourg O, Farcot JC, Margairaz A,
Bourdarias JP. Two- dimensional echocardiographic evaluation of right ventricular size and contractility in acute respiratory failure. Crit Care Med 1985; 13: 952-6.
16. Vieillard-Baron A, Schmitt JM, Augarde R, Fellahi JL, Prin
S, Page, et al. Acute cor pulmonale in acute respiratory
distress syndrome submitted to protective ventilation: incidence, clinical implications and prognosis. Crit Care Med
2001; 29: 1551-5.
17. Snow RL, Davies P, Pontoppidan H, Zapol WM, Reid L.
Pulmonary vascular remodeling in adult respiratory distress syndrome. Am Rev Respir Dis 1982; 126: 887-92.
18. Cook D, Attia J, Weaver B, McDonald E, Meade M,
Crowther M. Venous thromboembolic disease: an observational study in medical-surgical intensive care unit patients. J Crit Care 2000; 15: 127-32.
19. Vieillard-Baron A, Page B, Augarde R, Prin S, Qanadli S,
Beauchet A, et al. Acute cor pulmonale in massive pulmonary embolism: incidence, echocardiographic pattern,
clinical implications and recovery rate. Intensive Care Med
2001; 27: 1481-6.
20. Matthews JC, McLaughlin V. Acute right ventricular failure
in the setting of acute pulmonary embolism or chronic pulmonary hypertension: a detailed review of the pathophysiology, diagnosis, and management. Curr Cardiol Rev. 2008;
4: 49-59.
21. Furian T, Aguiar C, Prado K, Ribeiro RV, Becker L, Martinelli N, et al. Ventricular dysfunction and dilation in severe
sepsis and septic shock: relation to endothelial function
and mortality. J Crit Care. 2012; 27: 319, e9-15.
22. Chan CM, Klinger JR. The right ventricle in sepsis. Clin
Chest Med. 2008; 29: 661-76.
23. Markel TA, Wairiuko GM, Lahm T, Crisostomo PR, Wang
M, Herring CM, et al. The right heart and its distinct mechanisms of development, function, and failure. J Surg Res
2007; 146: 304 -13.
24. Methvin AB1, Owens AT, Emmi AG, Allen M, Wiegers SE,
Dries DL, et al. Ventilatory inefficiency reflects right ventricular dysfunction in systolic heart failure. Chest 2011;
139: 617-25.
25. Kevin LG, Barnard M. Right ventricular failure. Contin
Educ Anaesth Crit Care Pain 2007; 7: 89-94.
26. Kucher N, Walpoth N, Wustmann K, Noveanu M, Gertsch
M. QR in V1-an ECG sign associated with right ventricular
strain and adverse clinical outcome in pulmonary embolism. Eur Heart J. 2003; 24: 1113-9.
27. Miller GA, Sutton GC. Acute massive pulmonary embolism. Clinical and haemodynamic findings in 23 patients
studied by cardiac catheterization and pulmonary arteriography. Br Heart J 1970;32:518-23.
28. Reems MM, Aumann M. Central venous pressure: principles, measurement, and interpretation. Compend Contin
Educ Vet. 2012; 34: 1.
29. Greyson CR.Right heart failure in the intensive care unit.
Curr Opin Crit Care 2012; 18: 424-31.
30. Matthay MA, Chatterjee K. Bedside catheterization of the
Heart, Lung and Vessels. 2014, Vol. 6
Acute right heart syndrome in critical illness
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
pulmonary artery: risks compared with benefits. Ann Intern Med 1988; 109: 826.
Goldstein JA, Barzilai B, Rosamond TL, Eisenberg PR,
Jaffe AS. Determinants of hemodynamic compromise with
severe right ventricular infarction. Circulation 1990; 82:
359-68.
Zochios V, Wilkinson V. Assessment of intravascular fluid
status and fluid responsiveness during mechanical ventilation in surgical and intensive care patients. JICS 2011; 12:
295-300.
Wyler von Ballmoos M1, Takala J, Roeck M, Porta F, Tueller D, Ganter CC, et al. Pulse-pressure variation and hemodynamic response in patients with elevated pulmonary
artery pressure: a clinical study. Crit Care 2010; 14: 111.
Daudel F, Tüller D, Krähenbühl S, Jakob SM, Takala J.
Pulse pressure variation and volume responsiveness during
acutely increased pulmonary artery pressure: an experimental study. Crit Care 2010; 14: R122.
Michard F, Richards G, Biais M, Lopes M, Auler JO. Using
pulse pressure variation or stroke volume variation to diagnose right ventricular failure? Crit Care 2010; 14: 451.
Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher
MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report
from the American Society of Echocardiography endorsed
by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the
Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010; 23: 685-713; quiz 786-8.
Jardin F, Dubourg O, Guéret P, Delorme G, Bourdarias JP.
Quantitative two-dimensional echocardiography in massive pulmonary embolism: Emphasis on ventricular interdependence and leftward septal displacement. J Am Coll
Cardiol 1987; 10: 1201-6.
Hüttemann E. Transoesophageal echocardiography in critical care. Minerva Anestesiol. 2006; 72: 891-913.
Kang DK, Thilo C, Schoepf UJ, Barraza JM Jr, Nance JW Jr,
Bastarrika G, et al. CT signs of right ventricular dysfunction: prognostic role in acute pulmonary embolism. JACC
Cardiovasc Imaging. 2011; 4: 841-9.
Mitoff PR, Beauchesne L, Dick AJ, Chow BJ, Beanlands
RS, Haddad H, et al. Imaging the failing right ventricle.
Curr Opin Cardiol. 2012; 27: 148-53.
Lim W, Cook DJ, Griffith LE, Crowther MA, Devereaux
PJ. Elevated cardiac troponin levels in critically ill patients:
prevalence, incidence, and outcomes. Am J Crit Care 2006;
15: 280-88.
Cepkova M, Kapur V, Ren X, Quinn T, Zhuo H, Foster E,
et al. Clinical significance of elevated B-type natriuretic
peptide in patients with acute lung injury with or without
right ventricular dilatation: an observational cohort study.
Ann Intensive Care 2011;1:18.
Price LC, Wort SJ, Finney SJ, Marino PS, Brett SJ. Pulmonary vascular and right ventricular dysfunction in adult
critical care: current and emerging options for management: a systematic literature review. Crit Care 2010; 14:
169.
Piazza G, Goldhaber SZ. The acutely decompensated right
ventricle: pathways for diagnosis and management. Chest
2005; 128: 1836 -52.
Marik PE, Baram M, Vahid B. Does the central venous pressure predict fluid resposiveness? A systematic review of the
literature and the tale of seven mares. Chest 2008; 134: 172-8.
Marik PE, Cavallazzi R. Does the central venous pressure
predict fluid responsiveness? An updated meta-analysis
and a plea for some common sense. Crit Care Med. 2013;
41: 1774-81.
Mercat A, Diehl JL, Meyer G, Teboul JL, Sors H. Hemody-
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
namic effects of fluid loading in acute massive pulmonary
embolism. Crit Care Med. 1999; 27: 540-4.
Giglioli C, Landi D, Cecchi E, Chiostri M, Gensini GF,
Valente S, et al. Effects of ULTRAfiltration vs. DIureticS
on clinical, biohumoral and haemodynamic variables in
patients with deCOmpensated heart failure: the ULTRADISCO study. Eur J Heart Fail 2011; 13: 337-46.
Kerbaul F, Rondelet B, Motte S, Fesler P, Hubloue I,
Ewalenko P, et al. Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure.
Crit Care Med 2004; 32: 1035-40.
Luckner G, Mayr VD, Jochberger S, Wenzel V, Ulmer H,
Hasibeder WR, et al. Comparison of two dose regimens of
arginine vasopressin in advanced vasodilatory shock. Crit
Care Med 2007; 35: 2280-5.
Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008; 117: 1717-31.
Le Tulzo Y, Seguin P, Gacouin A, Camus C, Suprin E,
Jouannic I, et al. Effects of epinephrine on right ventricular
function in patients with severe septic shock and right ventricular failure: a preliminary descriptive study. Intensive
Care Med. 1997; 23: 664-70.
Kerbaul F, Rondelet B, Demester JP, Fesler P, Huez S, Naeije R, et al. Effects of levosimendan versus dobutamine on
pressure load-induced right ventricular failure. Crit Care
Med 2006; 34: 2814-9.
Morelli A, Teboul JL, Maggiore SM, Vieillard-Baron A,
Rocco M, Conti G, et al. Effects of levosimendan on right
ventricular afterload in patients with acute respiratory
distress syndrome: a pilot study. Crit Care Med 2006; 34:
2287-93.
Pathak A, Lebrin M, Vaccaro A, Senard JM, Despas F. Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. J Clin Pharm Ther. 2013; 38: 341-9.
Summerfield DT, Desai H, Levitov A, Grooms DA, Marik
PE. Inhaled nitric oxide as salvage therapy in massive pulmonary embolism: a case series. Respir Care. 2012; 57: 444-8.
Clapp LH, Finney P, Turcato S, Tran S, Rubin LJ, Tinker A.
Differential effects of stable prostacyclin analogs on smooth
muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol 2002; 26: 194-201.
Radermacher P, Santak B, Wust HJ, Tarnow J, Falke KJ.
Prostacyclin and right ventricular function in patients with
pulmonary hypertension associated with ARDS. Intensive
Care Med 1990; 16: 227-32.
Karakitsos D, Papanikolaou J, Karabinis A, Alalawi R,
Wachtel M, Jumper C, Alexopoulos D, et al. Acute effect of
sildenafil on central hemodynamics in mechanically ventilated patients with WHO group III pulmonary hypertension and right ventricular failure necessitating administration of dobutamine. Int J Cardiol. 2013; 167: 848-54.
Schmitt JM, Vieillard-Baron A, Augarde R, Prin S, Page B,
Jardin F. Positive end-expiratory pressure titration in acute
respiratory distress syndrome patients: impact on right
ventricular outflow impedance evaluated by pulmonary artery Doppler flow velocity measurements. Crit Care Med.
2001; 29: 1154-8.
Hakim TS, Michel RP, Chang HK. Effect of lung inflation
on pulmonary vascular resistance by venous and arterial
occlusion. J Appl Physiol 1982; 53: 1110-5.
Shekerdemian L, Bohn D. Cardiovascular effects of mechanical ventilation. Arch Dis Child 1999; 80: 475-80.
Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes
as compared with traditional tidal volumes for acute lung
injury and the acute respiratory distress syndrome. The
Heart, Lung and Vessels. 2014, Vol. 6
169
V. Zochios, et al.
170
64.
65.
66.
67.
68.
69.
70.
71.
Acute Respiratory Distress Syndrome Network. N Engl J
Med 2000; 342: 1301-8.
Balanos GM, Talbot NP, Dorrington KL, Robbins PA. Human pulmonary vascular response to 4 h of hypercapnia
and hypocapnia measured using Doppler echocardiography. J Appl Physiol 2003; 94: 1543-51.
Mekontso Dessap A, Charron C, Devaquet J, Aboab J,
Jardin F, Brochard L, et al. Impact of acute hypercapnia
and augmented positive end-expiratory pressure on right
ventricle function in severe acute respiratory distress syndrome. Intensive Care Med. 2009; 35: 1850-8.
Gattinoni L, Carlesso E, Langer T. Clinical review: Extracorporeal membrane oxygenation. Crit Care 2011; 15: 243.
Stratta C, Lavezzo B, Ballaris MA, Panio A, Crucitti M,
Andruetto P, et al. Extracorporeal membrane oxygenation
rescue therapy in a case of portopulmonary hypertension
during liver transplantation: a case report. Transplant Proc.
2013; 45: 2774-5.
Tiruvoipati R, Botha JA, Pilcher D, Bailey M. Carbon dioxide clearance in critical care. Anaesth Intensive Care 2013;
41: 157-62.
Teboul JL, Monnet X, Richard C. Weaning failure of cardiac origin: recent advances. Crit Care 2010; 14: 211.
Boeken U, Feindt P, Litmathe J, Kurt M, Gams E. Intraaortic
balloon pumping in patients with right ventricular insufficiency after cardiac surgery: parameters to predict failure of
IABP Support. Thorac Cardiovasc Surg. 2009; 57: 324-8.
Arafa OE, Geiran OR, Andersen K, Fosse E, Simonsen S,
72.
73.
74.
75.
76.
77.
Svennevig JL. Intraaortic balloon pumping for predominantly right ventricular failure after heart transplantation.
Ann Thorac Surg. 2000;70:1587-93.
Nordhaug D, Steensrud T, Muller S, Husnes KV, Myrmel
T. Intraaortic balloon pumping improves hemodynamics
and right ventricular efficiency in acute ischemic right ventricular failure. Ann Thorac Surg. 2004; 78: 1426-32.
Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG,
Hausleiter J, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012;
367: 1287-96.
Belohlavek J, Rohn V, Jansa P, Tosovsky J, Kunstyr J, Semrad M, et al.Veno-arterial ECMO in severe acute right ventricular failure with pulmonary obstructive hemodynamic
pattern. J Invasive Cardiol. 2010; 22: 365-9.
Gregoric ID, Chandra D, Myers TJ, Scheinin SA, Loyalka
P, Kar B. Extracorporeal membrane oxygenation as a bridge
to emergency heart-lung transplantation in a patient with
idiopathic pulmonary arterial hypertension. J Heart Lung
Transplant 2008; 27: 466-8.
Moazami N, Pasque MK, Moon MR, Herren RL, Bailey
MS, Lawton JS, et al. Mechanical support for isolated right
ventricular failure in patients after cardiotomy. J Heart
Lung Transplant. 2004; 23: 1371-5.
Berman M, Tsui S, Vuylsteke A, Klein A, Jenkins DP. Lifethreatening right ventricular failure in pulmonary hypertension: RVAD or ECMO? J Heart Lung Transplant 2008;
27: 1188-9.
Cite this article as: Zochios V, Jones N. Acute right heart syndrome in the critically ill patient. Heart, Lung and Vessels. 2014;
6(3): 157-170.
Source of Support: Nil. Disclosures: None declared.
Heart, Lung and Vessels. 2014, Vol. 6
ORIGINAL ARTICLE
Heart, Lung and Vessels. 2014; 6(3): 171-179
Atrial fibrillation after isolated
coronary surgery. Incidence, long
term effects and relation
with operative technique
C. Rostagno1, C. Blanzola2, F. Pinelli3, A. Rossi3, E. Carone2, P.L. Stefàno2
1
Department of sperimental and clinical medicine, University of Florence; 2Heart Surgery Unit AOU Careggi, Florence;
Cardio Anesthesiologic Unit, AOU Careggi, Florence
3
Heart, Lung and Vessels. 2014; 6(3): 171-179
ABSTRACT
Introduction: Postoperative atrial fibrillation after isolated coronary revascularization has been associated with
increased morbidity and mortality. Aim of present investigation was to evaluate incidence of postoperative atrial
fibrillation and its prognostic role in patients undergoing isolated coronary artery by-pass and disclose possible
differences between off-pump and cardiopulmonary assisted revascularization.
Methods: Prospective cohort study of 229 patients undergoing isolated coronary artery by-pass at a tertiary
heart surgery Centre. Off-pump treated patients were significantly older (70.5 vs 64.9 years, p<0.001). No other
baseline differences were found. Patients who developed postoperative atrial fibrillation were followed up for
an average period of 2 years.
Results: Post-operative occurred in 56/229 (24.1% after cardiopulmonary and 24.6% after off–pump coronary artery by-pass). Left atrium diameter was the only independent predictive factor (odds ratio =1.15, 95%
confidence interval 1.02-1.30, p<0.001). All patients with postoperative atrial fibrillation were treated and discharged in sinus rhythm, in 6/56 recurred, only in one persisted. One patient died during follow up. No stroke
was recorded.
Conclusions: After isolated surgical revascularization, atrial fibrillation occurred in 24% without differences
related to operative technique. Recurrence of atrial fibrillation occurred in 6/56 patients (10.7%) however only
in 1 persisted. Early and late mortality did not show relation with post-operative atrial fibrillation probably due
to immediate treatment with recovery of sinus rhythm before discharge.
Keywords: atrial fibrillation, cardiac revascularization, stroke, mortality.
INTRODUCTION
Atrial fibrillation occurs in 20-30% after surgical cardiac revascularization (1).
Several studies suggest that postoperative
Corresponding author:
Department of sperimental and clinical medicine
University of Florence
Viale Morgagni, 85
50134 Florence
e-mail: [email protected]
atrial fibrillation (POAF) is associated
with an increased duration of hospitalization, early and long term morbidity and
mortality (2, 3). Off-pump coronary artery
by-pass (CABG) grafting (OP-CABG) has
been hypothesized to decrease incidence of
POAF (4, 5); however contrasting results
has been reported (6, 7). Aim of present
prospective investigation was to evaluate
the incidence of POAF in patients undergoing isolated surgical revascularization in a
Heart, Lung and Vessels. 2014, Vol. 6
171
C. Rostagno, et al.
172
tertiary heart surgery centre. Patients with
POAF were followed for an average period
of 2 years to assess the recurrence rate of
the arrhythmia and its prognostic role on
early and late risk of stroke and mortality. Finally, the role of cardiopulmonary
by-pass (CPB) surgical revascularization
(CPB-CABG) and OP-CABG on POAF was
evaluated.
METHODS
Study population. Among 822 patients
who underwent heart surgery between
Jan 1 2009 and Dec 31 2009 in a tertiary
heart surgery Centre, 229 patients in sinus
rhythm on hospital admission (179 males,
50 females) underwent isolated CABG
(138 - OP-CABG, 91 - CPB-CABG). Patients
with atrial fibrillation, hyperthyroidism or
scheduled for Maze procedure were excluded from the study. In patients undergoing
isolated CABG, bipolar Maze procedure
was usually planned for subjects with persistent or frequent episodes of paroxysmal
atrial fibrillation. Finally, patients with
more than mild valvular disease and creatinine clearace <30 ml/min were excluded.
Echocardiographic evaluation was performed within 48 hours before surgery
using a Sequoia Acuson Instrument (Siemens Medical Solution, Mount View, CA,
USA). Echocardiography was performed
according to the guidelines of the American Society of Echocardiography (8). Clini-
Table 1 - Clinical and echocardiographic characteristics of patients included in the study mean (standard
deviation).
Overall
(229)
OP-CABG
(138)
CPB- CABG
(91)
p
Age (SD)
68.4 (9.2)
70.5 (8.6)
64.9 (9.0)
0.005
Sex M/F
179/50
101/37
78/13
0.06
Left atrium diameter (mm)
39.7 (4.6)
40.2 (4.6)
39.3 (4.5)
0.25
Left vetricular ejection fraction %
51.1(9.9)
50.7 (9.7)
51.6 (10.3)
0.66
Hypertension (%)
166 (72.5)
105 (76.1)
61 (67.0)
0.17
Hystory of atrial fibrillation (%)
6 (2.6)
5 (3.6)
1 (1.1%)
0.40
ACE Inhibitors or AT1 Blockers
169
107
62
0.12
Statins
160
99
61
0.46
` Blockers
118
74
44
0.14
P.O. Heart Rate (SD)
84.9 (19.9)
80.5 (12.9)
85.3 (14.3)
0.06
Systolic Blood Pressure mmHg (SD)
137 (23.5)
137.5 (19.5)
139 (20.0)
0.65
Diastolic Blood Pressure mmHg (SD)
68.5 (12.1)
66.9 (13)
70.8 (9.8)
0.07
Transient pace -maker stimulation
8
5
3
1
P.O bleeding (%)*
15
8
7
0.59
Hemodynamic impairment (%)**
16
11
5
0.61
Other (%)
11
6
5
0.75
Atrial Fibrillation (%)
56 (24,4)
34 (24.6)
22 (24.1)
0.9
Length of Hospitalization (Days)
5.7 (4.5)
5.7 (4.8)
5.6 (4.1)
0.94
*Bleeding requiring transfusion at least 2 units of packed red blood cells or surgical revision.
**Hemodynamic deterioration with the need to infuse amines.
OP = off pump; CPB = cardipulonary-by pass; CABG = coronary artery by-pass; SD= standard deviation.
Heart, Lung and Vessels. 2014, Vol. 6
Atrial fibrillation after CABG
173
Table 2 - Clinical diagnosis, number of diseased vessels and grafts performed.
Clinical diagnosis
Overall
229
OP-CABG
138
CPB-CABG
91
p
Chronic CAD
167
98
69
0.67
ACS
59
39
20
0.35
3
1
2
0.56
Elective surgery
STEMI
160
96
64
0.64
Urgency
61
37
24
0.9
Emergency
8
5
3
0.86
3 vessels
99
64
35
0.22
3 vessel + LMC
58
32
26
0.65
LMC
35
20
15
0.71
2 vessels
17
10
7
0.9
2 vessels + LMC
8
5
3
0.85
1 vessel
10
7
5
0.79
Diseased vessels
By-pass conduit
LIMA
18
11
7
0.87
LIMA+ RIMA
50
29
21
0.74
LIMA + saph
94
61
33
0.27
LIMA+ RIMA + saph
67
37
30
0.37
OP = off pump; CABG = coronary artery by-pass; CAD = coronary artery disease; ACS = acute coronary
syndrome; STEMI = elevated ST acute myocardial infarction ; LMC = left main coronary; LIMA = left
internal mammary artery; RIMA = right internal mammary artery; saph = saphene vein.
cal and echocardiographic characteristics
of patients are reported in Table 1. In Table
2 clinical diagnosis, indications for surgery
(elective, urgency/emergency), the number
of diseased vessels and graft performed in
the groups under investigation are reported. Thirty clinical and echocardiographic
variables were considered to evaluate a relationship with occurrence of POAF.
After surgery all patients were continuously monitored electrocardiography (ECG),
blood pressure, non-invasive oxygen saturation for at least the first 48 hours. ECG
monitoring, both at bed and by telemetry,
was maintained until discharge. Transient electric stimulation through epicardic
wires was used for severe bradycardia or
atrio-ventricular (AV) block until restoration of heart rhythm. All symptomatic ar-
rhythmic episodes or asymptomatic atrial
fibrillation lasting more than 15 minutes at
ECG monitoring were considered as POAF
and included in the analysis. Patients who
did not recover sinus rhythm (SR) within
30 minutes were usually treated with intravenous amiodarone (300 mg in 1 hour
followed by 900 mg/24 h e.v. continuous
infusion) to control heart rate. Electrical
cardioversion was considered when sinus
rhythm was not restored within 24 hours
after the beginning of pharmacological
treatment. Amiodarone was continued for
3 months after discharge. Perioperative
complications including bleeding needing
transfusion of at least 2 units of packed red
blood cells and/or surgical revision, severe
hypotension requiring amines (norepinephrine, epinephrine, dobutamine or do-
Heart, Lung and Vessels. 2014, Vol. 6
C. Rostagno, et al.
174
pamine), and new onset AV block or severe
bradycardia requiring electrical stimulation were recorded. Postoperative pericardial inflammation was diagnosed in the
presence of pericardial rubs and/or ECG
or echocardiogram signs of pericardial involvement. In the end, duration of hospitalization was examined. All patients was
discharged to rehabilitation facilities. The
study was approved by the ethic committee
of our Institution and all participants gave
their informed consent.
Follow-Up. Only patients with POAF were
followed-up and entered the study. Followup visit were scheduled after 3, 12 and 24
months. Holter monitoring was performed
every 3 months during the first year and
thereafter every 6 months. Follow-up was
closed on December 31 2012. No patient
was lost at follow-up. Primary end point of
the study was the evaluation of recurrence
of atrial fibrillation and related hospitalization; secondary end points were all cause
hospitalization and mortality. Finally we
evaluated the role of surgical technique
(CPB-CABG vs OP-CABG) on POAF.
Statistical Analysis. Data were described as
mean and standard deviation (SD) for continuous variables and as number and percent for categorical variables. Preoperative
and operative patient characteristics were
compared according to the occurrence of
postoperative AF by means of the Student t
test or Fisher exact test for continuous and
categorical variables, respectively, or finally by ANOVA. Multivariate logistic regression analysis was used to evaluate independent risk factors for atrial fibrillation.
RESULTS
In-Hospital Outcomes. Overall incidence of
POAF during hospitalization was 24.4%
(56 of 229 patients), 38 males and 18 females. 1/229 patients died after surgery.
Patients who developed AF after surgery
were older than ones in stable sinus rhythm
(70.5 vs 64.9 years, p=0.005). POAF was
not related to clinical indication to surgery
(elective vs urgency/emergency), number of diseased vessels or graft performed
(Table 3). Postoperative troponin release
did not differ between two groups. In patients with POAF left ventricular ejection fraction was not significantly lower
than in sinus rhythm group (49% vs 51%).
Two out of six patients with paroxysmal
atrial fibrillation before surgery developed
POAF. The use of beta-blockers, angiotensin converting enzyme (ACE) inhibitors/
angiotensin A1 receptor (AT1) blockers
and statins did not influence the prevalence of postoperative AF. Patients with
AF did not show a different prevalence
of intra-aortic balloon pump use or treatment with vasopressors or inotropic drugs
after surgery. Transient electric stimulation after surgery was needed in 2 patients
with POAF and in 3 who did not develop
arrhythmias. No permanent pacing was
required. Multivariate analysis revealed
that only antero-posterior left atrium diameter was associated with an increased
risk of POAF (odds ratio = 1.15; 95% confidence interval (CI) [1.02, 1.30], p<0.001)
(Table 4). The frequency of POAF was not
statistically different between patients undergoing OP-CABG and those undergoing
cardiopulmonary by-pass (24.6% for OPCABG vs 24.1% for CPB-CABG.) Table 3
reports the relative number of elective in
comparison to urgency/emergency procedures, and the number of grafts conduits
employed in the two groups. Patients with
POAF undergoing OP-CABG were on average 7 years older than CBP- CABG (74.3
vs 67 years, p<0.001). There were no other
significant differences between the two
groups. All patients with atrial fibrillation
were successfully treated and discharged
in sinus rhythm. Length of hospitalization
Heart, Lung and Vessels. 2014, Vol. 6
Atrial fibrillation after CABG
was on average 2 days longer in patients
with POAF after CPB-CABG.
Follow-up results. The 56 patients with
postoperative atrial fibrillation were followed-up for a median of 685 days. 6 male
patients, had recurrence of atrial fibrillation (10.7%). Age was not significant dif-
ferent in those patients (average age 72.5
vs 71.3 years). Among those patients, three
underwent OP-CABG, and the others CPBCABG. Preoperative left ventricular ejection fraction was not different in patients
with AF in comparison to patients without
recurrence (48% vs 49%), while mean left
Table 3 - Comparison of clinical, echocardiographic characteristics and conduits used for grafting between patients
with and without POAF according to surgical technique.
Mean (standard deviation)
POAF (56)
OP (34)
CPB (22)
p
74.3 (6.7)
67 (9.5)
0.001
22/12
16/6
0.57
Left atrium diameter (mm)
43.4 (4.5)
40.3 (5.3)
0.001
Left ventricular ejection fraction %
48 (10.2)
50.2 (9.1)
0.46
28
12
0.07
Age. Years
Sex M/F
Hypertension
Hystory of atrial fibrillation
2
0
0.51
ACE Inhibitors or AT1 Blockers
27
10
0.08
Statins
22
13
0.77
` Blockers
22
13
0.77
P.O. Heart Rate (SD)
82.8 (16.9)
85.35 (16.01)
0.51
Sistolic Blood Pressure mmHg (SD)
139.3 (16.1)
134 (17.8)
0.27
66. 6 (9.4)
69.8 (11.1)
0.23
2
0
0.51
Diastolic Blood Pressure mmHg (SD)
Transient pace-maker stimulation
P.O bleeding (%)*
3
5
0.14
Hemodynamic impairment (%)**
3
0
0.46
15
0.77
CLINICAL CONDITION
COPD
1
Chronic CAD
21
Acute Coronary Syndrome
11
7
0.8
STEMI
1
1
1
Left Internal Mammary Artery
2
3
0.37
LIMA + RIMA
10
7
0.9
LIMA + SAPH.
18
9
0.78
LIMA+RIMA +Saphen vein
4
3
0.9
5.9 (3.6)
7. 5 (6.8)
0.25
By-Pass Conduit
Length of Hospitalization (Days)
*Bleeding requiring transfusion at least 2 units of packed red blood cells or surgical revision.
** Hemodynamic deterioration with the need to infuse amines.
POAF = postoperative atrial fibrillation; OP = off pump; CPB = cardipulonary-by pas; COPD = chronic
obstructive pulmonary disease; CAD = coronary artery disease; ACS = acute coronary syndrome; STEMI =
elevated ST acute myocardial infarction ; LMC= left main coronary; LIMA = left internal mammary artery,
RIMA = right internal mammary artery, SAPH = saphen vein; SD = stabdard deviation.
Heart, Lung and Vessels. 2014, Vol. 6
175
C. Rostagno, et al.
176
Table 4 - Risk factors for POAF. Logistic regression analysis.
age
sex
election vs urgencyemergency
LA diameter
`-blockers
ACE inhibitors
statins
heart rate
LV ejection fraction
Systolic BP
Diastolic BP
troponin peak
serum potassium
OD
95% CI
0,95
1.08
1.18
1,15
2,47
0,52
0,41
1,00
0.99
1,02
0,96
0,96
1,20
0,90 1,01
0.95 -1.18
0,44 - 2,21
1,02 - 1,30
0,85 - 7,14
0,15 - 1,76
0-13 – 1.2
0.98 – 1.03
0.94 – 1.05
0.99 – 1.04
0.92 - 1.01
0.85 – 1.08
0.89 – 1.64
p
0.14
0.18
0.72
0.01
0.09
0.29
0.12
0.49
0.97
0.11
0.15
0.51
0.22
OD = odds ratio; CI = confidence interval; LA = left atrium; ACE = angiotensin-converting-enzyme; LV =
left ventricle; BP = blood pressure.
atrium anterior-posterior diameter was respectively 42 mm and 40 mm.
On average, the AF recurrences occurred
within 60 days after discharge. Amiodarone treatment was successful in 3 patients, electric cardioversion in one case. In
one patient sinus rhythm recovered spontaneously.
Ultimately, in the last patient sinus rhythm
could not be restored. At the end of follow
up only one patient died not for cardiovascular cause (lung cancer).
DISCUSSION
Incidence of atrial arrhythmias after cardiac surgery has been reported to range
from 10 to 65% (9, 10). According to a large
multi-centre study, POAF after CABG occurs in near 30% (11). Several factors, including type of surgical procedure, patient
demographics, criteria used for diagnosis
and methods of ECG monitoring, may account for the wide range of POAF incidence reported in literature. Several mechanisms are involved in the pathogenesis of
POAF. Dispersion in atrial refractoriness
induces multiple local re-entry wavelets;
therefore, atrial fibrillation may be induced
by several factors. Among these: trauma
from surgical dissection and manipulation,
myocardial ischemic damage, an exaggerated local inflammatory response with or
without pericarditis, an elevation in atrial
pressure from post-operative ventricular
stunning a chemical stimulation due to
postoperative support with catecholamine
and other inotropic agents, a reflex sympathetic activation from volume loss, anemia
or pain, parasympathetic activation, fever
from atelectasis or infection, hypoglycaemia, metabolic and electrolyte imbalance,
fluid overload, prolonged post operative
electrical stimulation.
Cardiopulmonary by-pass related hemodynamic changes may induce intraoperative
atrial ischemia that has been hypothesized
to play a role in the development of POAF.
Evidence supporting an association between AF after CABG surgery and late
mortality is conflicting. Few data of patients with POAF after hospital discharge
are available. Almassi et al. (3) reported
at 6 months after surgery a significantly
higher mortality in AF patients compared
Heart, Lung and Vessels. 2014, Vol. 6
Atrial fibrillation after CABG
with patients without AF (9.4% vs 4.2%).
Villareal et al. (2) showed in 6475 patients
undergoing first isolated CABG that POAF
was associated with at increased risk of
death (odds ratio =1.5; 95% CI [1.3, 1.8]).
In this study, cumulative survival rate at
1 and 4 years was 87% and 74% in POAF
patients versus 94% and 87% for non-AF
population. In more than 8500 isolated
CABG patients a significantly increased
risk of death was observed among those
who developed postoperative AF compared
with those who did not (odds ratio =1.2;
95% CI, 1.1 to 1.3) (11). Patients affected
by postoperative AF had an increased
1-year mortality (4.6% versus 2.0%), and
AF was confirmed to independently predict late mortality (hazard ratio, 1.7; 95%
CI [1.2, 2.5]) (10). Results from present investigation do not support an association
of POAF with an increase of late mortality
in patients undergoing surgical revascularization. Only one patient died at 2 years
follow-up and not for cardiovascular cause.
Restoration of sinus rhythm in all patients
during hospitalization and low recurrence
rate may have significantly decreased
the risk of mortality, in particular due to
stroke or complications of oral anticoagulant treatment.
Decreased risk of ischemic damage in beating heart CABG has been suggested to reduce incidence of POAF. Initial favourable
results (6, 7) has not been confirmed by
other authors (4, 12). Siebert et al (5) during
the postoperative intensive care unit stay
reported a 9.8% rate of POAF in patients
after CPB-CABG, 10.2% after OP-CABG,
and 21% after CABG combined with valve
replacement. A recent meta-analysis suggested a decreased incidence of AF in OPCABG although overall mortality was not
affected (13).
A not significant difference in the incidence of POAF between the two techniques was reported by several other stud-
ies (14, 15). Two randomized, controlled
trials and one large scale concurrent cohort study addressed the issue of beatingheart CABG. Ascione et al (7) found a significantly lower rate of postoperative AF
in the OP-CABG group (11.0%) than in the
CBP-pump CABG group (45.0%) in 200
patients who had been randomized to undergo CABG either with or without CPB.
A significant difference in postoperative
AF favouring the OP-CABG group (21.2%)
compared to the on-pump CABG group
(6.3%) was reported by Hernandez et al
(16). In contrast, in 281 patients randomized to CABG with or without CPB, Van
Dijk et al (9) reported no difference in the
rate of postoperative AF.
In patients undergoing emergency revascularization for acute coronary syndromes
off-pump surgery vs CPB surgery was performed in patients with more severe clinical conditions: OP-CABG patients were
more frequently in cardiogenic shock, had
an impaired renal function, a log EUROSCORE >20 or a left ventricular ejection
fraction <30% (17). Overall survival and
event rate, however, were similar at 5 five
year follow-up. Postoperative AF occurred
in 30.2% patients undergoing CPB-CABG
vs 29.3% in OP-CABG surgery while the
incidence of stroke was two-fold in the
former group (6.7 vs 2.5%, p<0.035). Noteworthy the incidence of AF was two folds
in patients with cardiogenic shock undergoing CPB versus OP surgery (62.5 vs 39.8%),
with a significant increase in the number
of stroke (33.3 vs 9.6%, p<0.009). Recently
a TnI serum concentration >0.901 ng/ml
at ICU admission has been identified as cutoff value for prediction of AF in patients
undergoing elective CABG (18). Patients
with serum TnI > of 0.901 ng/ml showed
an 11.5 times increased risk for the onset of
AF after elective CABG. In present investigation no significant relation was found between TnI serum concentration after sur-
Heart, Lung and Vessels. 2014, Vol. 6
177
C. Rostagno, et al.
178
gery and the risk of AF (odds ratio =0,9695% CI [0,85, 1,08], p=0.17).
In our experience, the incidence of POAF
resulted not significantly different in patients undergoing OP-CABG in comparison
to CPB-CABG. The two groups were comparable for severity of coronary disease,
number of grafts performed and clinical
presentation (urgent versus elective surgery). However, mean age of patients undergoing OP-CABG was on average 7 years
older in comparison to patients treated
with CPB-CABG.
erative AF is associated with an increased
late mortality, rate of stroke or rehospitalization. Restoration of sinus rhythm before
hospital discharge may have significantly
limited the negative prognostic effects of
post operative atrial fibrillation.
At present, the guidelines of the American
College of Chest Physician state that OPCABG cannot be recommended to decrease
postoperative AF because of conflicting results resulted from randomized controlled
trials or large-scale concurrent cohort studies (20).
Limitations
The present study was limited by its observational nature, by a relative short followup period (2 years), and by the low number
of patients investigated. In addition, patients were not randomized to either treatment. Otherwise the short time of enrolment (1 year), the similar characteristics
of the two groups, with the cited exception
of age, and the limited number of operators decreased the risk of non homogeneity of the population under investigation.
The low number of recurrences occurred,
similarly to other studies, may be related to
potential bias due to the reliance on self-reporting for follow-up cardiac rhythm data.
Although scheduled Holter monitoring in
our investigation did not reveal paroxysmal episodes of atrial fibrillation, only continuous monitoring systems may provide
definitive data. Similarly, the use of questionnaires and clinical examination during follow-up may not accurately identify
paroxysmal episodes of AF and may potentially have underestimated the incidence of
the arrhythmia recurrences.
REFERENCES
CONCLUSION
Despite the reported limitations, our study
does not support the hypothesis that postop-
1. Hravnak M, Hoffman LA, Saul MI, Zullo TG, Whitman
GR. Resource utilization related to atrial fibrillation after
coronary artery bypass grafting. Am J Crit Care. 2002; 11:
228-38.
2. Villareal RP, Hariharan R, Liu BC, Kar B, Lee VV, Elayda
M, et al. Postoperative atrial fibrillation and mortality after
coronary artery bypass surgery. J Am Coll Cardiol. 2004;
43: 742-48.
3. Almassi GH, Schowalter T, Nicolosi AC, Aggarwal A,
Moritz TE, Henderson WG, et al. Atrial fibrillation after
cardiac surgery: a major morbid event? Ann Surg. 1997;
226: 501-11.
4. Buffolo E, de Andrade JCS , Branco JN, Teles CA, Aguiar
LF, Gomes WJ. Coronary artery bypass grafting without cardiopulmonary bypass. Ann Thorac SurAg 1996; 61: 63-6.
5. Siebert J, Anisimowicz L, Lango R, Rogowski J, Pawlaczyk
R, Brzezinski M, et al. Atrial fibrillation after coronary artery bypass grafting: does the type of procedure influence
the early postoperative incidence? Eur J Cardiothorac Surg.
2001; 19: 455-9.
6. Stamou SC, Dangas G, Hill PC, Pfister AJ, Dullum MK,
Boyce SW, et al. Atrial fibrillation after beating heart surgery. Am J Cardiol. 2000; 86: 64-7.
7. Ascione R, Caputo M, Calori G, Lloyd CT, Underwood MJ,
Angelici GD. Predictors of atrial fibrillation after conventional and beating heart coronary surgery: a prospective,
randomized study. Circulation. 2000; 102: 1530-5.
8. Douglas PS, Khandheria B, Stainback RF, et al. ACCF/
ASE/ACEP/ASNC/SCAI/SCC/SCMR 2007 appropriateness criteria for transthoracic and transesophageal echocardiography: a report of the American College of Cardiology
Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American Society of
Echocardiography, American College of Emergency Physicians, American Society of Nuclear Cardiology, Society for
Cardiovascular Angiography and Interventions, Society of
Cardiovascular Computed Tomography, and the Society
for Cardiovascular Magnetic Resonance. Endorsed by the
American College of Chest Physicians and the Society of
Critical Care Medicine. J Am Soc Echocardiogr. 2007; 20:
787-805.
9. van Dijk D, Nierich AP, Jansen EW, Nathoe HM, Suyker
WJ, Diephuis JC, at al. Octopus Study Group. Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study. Circulation 2001;
104: 1761-6.
Heart, Lung and Vessels. 2014, Vol. 6
Atrial fibrillation after CABG
10. Mathew JP, Parks R, Savino JS, Friedman AS, Koch C,
Mangano DT, et al. Atrial fibrillation following coronary
artery bypass graft surgery: predictors, outcomes, and resource utilization: Multicenter Study of Perioperative Ischemia Research Group. JAMA. 1996; 276: 300-6.
11. Mathew JP, Fontes ML, Tudor IC, Ramsay J, Duke P, Mazer CD, et al. A multicenter risk index for atrial fibrillation
after cardiac surgery. JAMA. 2004; 291: 1720-9.
12. Cohn WE, Sirois CA, Johnson RG. Atrial fibrillation after
minimally invasive coronary artery bypass grafting: a retrospective, matched study. J Thorac Cardiovasc Surg 1999;
117: 298-301.
13. Moller CH, Penninga L, Wetterslev J, Steinbruchel DA. Offpump versus on pump coronary artery bypass grafting for
ischaemic heart disease. Cochrane Database Syst Rev. 2012
Mar 14; 3: CD007224.
14. Abreu JE, Reilly J, Salzano RP, Khachane VB, Jekel JF,
Clyne CA. Comparison of frequencies of atrial fibrillation
after coronary artery bypass Am J Cardiol. 1999; 83: 775-6.
15. Banach M, Goch A, Misztal M, Rysz J, Zaslonka J, Goch JH,
et al. Relation between postoperative mortality and atrial
fibrillation before surgical revascularization: 3-year followup. Thorac Cardiovasc Surg. 2008; 56: 20-3.
16. Hernandez F, Cohn WE, Baribeau YR, Tryzelaar JF,
17.
18.
19.
20.
Charlesworth DC, Clough RA, et al. In-hospital outcomes
of off-pump versus on-pump coronary artery bypassprocedures: a multicenter experience. Ann Thorac Surg. 2004;
78: 1528-34.
Rastan AJ, Eckenstein JI, Hentschel B, Funkat AK, Gummert JF, Doll N, et al. Emergency coronary artery bypass
graft surgery for acute coronary syndrome: beating heart
versus conventional cardioplegic cardiac arrest strategies.
Circulation. 2006; 114 (Suppl. I): 477-85.
Leal JC, Petruccic O, Godoya MF, Brailea ML. Perioperative
serum troponin I levels are associated with higher risk for
atrial fibrillation in patients undergoing coronary artery bypass graft surgery. Intern CardioVascular and Thorac. Surg.
2012; 14: 22-25
Mahoney EM, Thompson TD, Veledar E, Williams J, Weintraub WS. Cost-effectiveness of targeting patients undergoing cardiac surgery for therapy with intravenous amiodarone to prevent atrial fibrillation. J Am Coll Cardiol. 2002;
40: 737-45.
Creswell LL, Alexander JC, Ferguson B, Lisbon A, Fleisher
LA. Intra operative interventions: American College of
Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac
Surgery. Chest. 2005; 128 (Suppl. 2): 28-35.
Cite this article as: Rostagno C, Blanzola C, Pinelli F, Rossi A, Carone E, Stefàno PL. Atrial fibrillation after isolated coronary
surgery. Incidence, long term effects and relation with operative technique. Heart, Lung and Vessels. 2014; 6(3): 171-179.
Source of Support: Nil. Disclosures: None declared.
Heart, Lung and Vessels. 2014, Vol. 6
179
ORIGINAL ARTICLE
Heart, Lung and Vessels. 2014; 6(3): 180-186
180
Acute myocardial infarction
associated to DPP-4 inhibitors
J.P.L. Nunes1,2, J.D. Rodrigues2, F. Melão2
1
Faculdade de Medicina da Universidade do Porto, Portugal; 2Department of Cardiology, Hospital Sao Joao, Porto, Portugal
Heart, Lung and Vessels. 2014; 6(3): 180-186
ABSTRACT
Introduction: Diabetes mellitus is associated with cardiovascular disease. Anti-diabetic therapy has a limited
capability (if any) of changing the incidence of either death or major cardiovascular disease, and cardiovascular
safety concerns have been raised. We aimed at identifying episodes of acute myocardial infarction associated to
a relatively new class of drugs, dipeptidyl peptidase-4 inhibitors.
Methods: Retrospective study: from 954 admissions (15 month period) in the coronary care unit, we selected
200 admissions corresponding to 196 patients with myocardial infarction and diabetes. 35 of these patients were
receiving therapy with dipeptidyl peptidase-4 inhibitors (the vast majority, in association to metformin). We
evaluated the peak plasma cardiac troponin I as the main study parameter.
Results: Patients on dipeptidyl peptidase-4 inhibitors therapy had a mean peak cardiac troponin plasma level of
50.2±121.3 ng/ml (n=35), the corresponding value for insulin being 39.2±108.4 ng/ml (n=56), for metformin
the value was 45.8±97.3 ng/ml (n=93) and for sulfonylureas, 42.4±77.7 ng/ml (n=52). None of these values
differed significantly from the corresponding control group of patients not taking each class of drug. The linear
regression study also yielded a negative result relating therapy with dipeptidyl peptidase-4 inhibitors and peak
troponin values. Acute myocardial infarctions associated to dipeptidyl peptidase-4 inhibitors varied widely in
the clinical characteristics of the patients.
Conclusions: We found no evidence that peak plasma troponin I was different between patient with acute myocardial infarction and use of dipeptidyl peptidase-4 inhibitors when compared to cases not under such therapy.
Keywords: acute myocardial infarction, diabetes mellitus, dipeptidyl peptidase-4 inhibitors, metformin, troponin.
INTRODUCTION
Diabetes mellitus is a highly prevalent disease that acts as a cardiovascular risk factor (1). The presence of diabetes mellitus is
associated with an increase in the mortality rate of patients, both with or without a
previous myocardial infarction (2). Diabetes mellitus has been shown to be associated to an increased incidence of coronary
Corresponding author:
José Pedro L. Nunes
Faculdade de Medicina da Universidade do Porto
Alameda Prof. Hernani Monteiro
4200 Porto, Portugal
e-mail: [email protected]
artery disease and stroke (3). Clinical trials
have shown anti-diabetic therapies to have
very limited, if any, capability to change the
incidence of either death or major cardiovascular disease, such as myocardial infarction or stroke (4). Issues of cardiovascular
safety associated to anti-diabetic therapy
have been put forward (5).
Dipeptidyl peptidase-4 inhibitors (DPP4 inhibitors) are a relatively new class of
anti-diabetic drugs that have been shown
to decrease glycated hemoglobin, either if
used alone or in association to other drugs
such as metformin.
In patients with myocardial infarction, the
Heart, Lung and Vessels. 2014, Vol. 6
Myocardial infarction and DPP-4 inhibitors
presence of diabetes mellitus is relatively
common. In the present investigation, we
aimed to characterize episodes of acute
myocardial infarction associated to the use
of DPP-4 inhibitors, as well as to other antidiabetic drugs. For that purpose, data from
the admissions that took place during 15
months in an acute coronary care unit were
retrospectively evaluated. Peak plasma cardiac troponin I was the major parameter
under study, since plasma troponin provides an estimate of the importance of the
myocardial injury in myocardial infarction
(6).
METHODS
The present study was retrospective. From
all patients admitted to an intensive coronary care unit from January 2011 to March
2012, patients with both acute myocardial
infarction and diabetes mellitus were identified. A patient was considered to have diabetes mellitus if anti-diabetic therapy was
being taken, if the diagnosis had been previously established on the basis of current
recommendations (7) or if glycated hemoglobin greater than 6.5% (7) was present
at admission.
Acute myocardial infarction was diagnosed
following the recommendations in use (8).
Patients with in-hospital acute myocardial
infarction were excluded. Patients who
were initially admitted to another hospital,
and who were later transferred into our
institution were only included if the peak
value for plasma troponin I could be clearly
identified.
Data on previous anti-diabetic drug use
was searched in the electronic file(s) corresponding to each patient. Peak plasma
cardiac troponin I levels was also searched
in the corresponding electronic files. Additional data were obtained for each patient
on the following parameters: presence of ST
segment elevation in the electrocardiogram;
previous history of myocardial infarction;
previous coronary revascularization, either
percutaneous or surgical; primary coronary
angioplasty in the current episode; plasma
creatinine at admission.
Peak cardiac troponin levels in patients under anti-diabetic therapy with DPP-4 inhibitors were compared to the corresponding
values for patients under no such therapy.
The same comparison was carried out regarding insulin, metformin and sulfonylureas.
Troponin I was measured using the ARCHITECT STAT system, of Abbott Diagnostics (Abbott Park, Illinois, USA). The
99th percentile of troponin I in a normal
population with this assay was established
at 0.012 ng/ml.
The present protocol was approved by the
ethics committee of our institution.
Statistical Methods. Data are presented as
arithmetic means and standard deviations.
Pairs of means were compared using Mann
Whitney U test. Linear regression analysis
was carried out, taking peak plasma troponin I as dependent variable, and age, sex,
plasma creatinine at admission, presence
of ST segment elevation and use of DPP-4
inhibitors, use of metformin, use of insulin
and use of a sulfonylurea as independent
variables.
For all comparisons a two-sided significance
level of 0.05 was considered statistically
significant. Data analysis was performed
using the SPSS 20 software program, from
IBM.
RESULTS
A total number of 954 patients were admitted in the period under study. From those,
200 admissions, corresponding to 196 patients (2 patients were admitted twice and
1 patient for three different times), were
Heart, Lung and Vessels. 2014, Vol. 6
181
J.P.L. Nunes, et al.
182
Table 1 - Arithmetic mean and standard deviation (STD) for peak troponin I plasma values for patients with
diabetes mellitus and acute myocardial infarction.
Mean
STD
N
Mean
STD
N
SL
DPP-4i
50.2
121.3
35
No DPP-4i
44.5
85.5
145
0.32
Insulin
39.2
108.4
56
No insulin
52.1
89.3
144
0.11
Metformin
45.8
97.3
93
No metformin
45.3
89.1
87
0.99
Sulfonylurea
42.4
77.7
52
No sulfonylurea
47.8
99.2
128
0.91
N = number; SL = significance level (Mann-Whitney U test); DPP-4i = dipeptidyl peptidase-4 inhibitors.
selected as meeting the inclusion criteria.
127 patients were of the male sex and 69
were female. The mean age was 67.7±10.6
years. ST segment elevation myocardial
infarction was present in 62 patients. Primary coronary angioplasty was carried out
in 44 patients.
The mean peak plasma cardiac troponin I values for the 200 admissions was
48.5±94.9 ng/ml.
DPP-4 inhibitors (either vildagliptin or sitagliptin) were being taken on admission by
35 patients, insulin by 56 patients, metformin by 93 patients, and sulfonylureas by 52
patients. A small number of patients were
taking other types of antidiabetic dugs. 31
patients were taking no antidiabetic therapy at admission. Nineteen patients were
taking oral antidiabetic drugs, but it was
impossible to establish which drugs were in
use (either the patients did not recall the
names of the drugs in use or the record was
incomplete).
As for the most commonly found specific anti-diabetic therapies the following
mean values for peak plasma troponin
I (in ng/ml) were seen: no anti-diabetic therapy, 68.6±93.1 (n=31); insulin
alone 22.8±70.7 (n=37), metformin
alone 48.9±98.5 (n= 31), sulfonylurea
alone 106.9±166.5 (n=7), sulfonylurea
plus metformin 27.9±38.2 (n=17); DPP4 inhibitors plus metformin 32.7±50.8
(n=14).
The mean value for peak plasma tropo-
nin for patients either taking or not taking DPP-4 inhibitors, insulin, metformin
or sulfonylureas are shown in Table 1.
Patients under DPP-4 inhibitors therapy
had a mean peak cardiac troponin plasma level of 50.2±121.3 ng/ml (n=35),
the corresponding value for insulin being
39.2±108.4 ng/ml (n=56), for metformin
the value being 45.8±97.3 ng/ml (n=93)
and for sulfonylureas, 42.4±77.7 ng/ml
(n=52). None of these values was significantly different from the corresponding
group of patients not taking each class of
drug (Table 1). As Table 2 shows, almost all
(32/35) patients under DPP-4 inhibitors
were simultaneously using metformin, and
many were using other anti-diabetic drugs.
Linear regression analysis, taking peak
plasma troponin I as dependent variable,
and age, sex, plasma creatinine at admission, ST segment elevation and use of
DPP-4 inhibitors as independent variables,
yielded an overall significant result (ANOVA with F 5.1, significance level <0.01),
however only the presence of ST segment
elevation reached a significance level
<0.05 (the presence of DPP-4 inhibitors
had a significance level of 0.35).
Table 2 shows some clinical characteristics
of patients with acute myocardial infarction admitted while currently taking DPP4 inhibitors. Eight cases of elevated ST-segment infarction, including one case of intra-stent thrombosis, and a case with new
left bundle branch block were seen. One
Heart, Lung and Vessels. 2014, Vol. 6
Myocardial infarction and DPP-4 inhibitors
Table 2 - Clinical characteristics of 35 patients with diabetes mellitus and acute myocardial infarction associated to the use of DDP-4 inhibitors. Plasma creatinine (mg/dL); troponin I (ng/mL).
Age
(years)
Sex
Peak
Plasma
Troponin I Creatinine
ST
segment
Previous Previous Primary
CABG/PCI
AMI
PCI
Antidiabetic therapy
61
Male
0.182
0.9
58
Female
121.5
0.9
71
Male
0.174
1.3
61
Male
5.17
0.7
Vildagliptin/metformin
76
Female
4.8
1.1
Vildagliptin/metformin
Sitagliptin/metformin
New LBBB
1
1
Vildagliptin/metformin; insulin
Sitagliptin/metformin
60
Male
1
1.5
Sitagliptin/metformin; other OAD
67
Female
38
1.1
Sitagliptin/metformin
73
Male
11.8
0.8
Vildagliptin/metformin; gliclazide; acarbose
72
Female
0.26
0.9
Vildagliptin/metformin; glimepiride
66
Male
64
1.1
Vildagliptin/metformin
66
Male
3.25
1
Sitagliptin/metformin
76
Male
18.28
0.9
PCI
1
Sitagliptin; gliclazide; pioglitazone
76
Female
3.77
0.6
CABG
1
Sitagliptin
54
Male
28.09
0.5
79
Female
75.8
0.9
PCI
1
62
Male
0.179
0.8
63
Male
0.47
1.1
82
Female
0.048
1
61
Female
0.36
0.9
67
Male
2.01
2.4
81
Male
5.69
0.8
CABG
Sitagliptin; metformin; glibenclamide
78
Female
11.3
0.9
PCI
Sitagliptin; glibenclamide/metformin
51
Male
77.7
0.7
78
Male
0.704
1
75
Male
26
0.8
Elevated
61
Male
691
1.2
Elevated***
72
Male
0.141
1
60
Male
24
0.7
86
Male
0.309
1.1
CABG
69
Male
0.388
0.6
PCI
Sitagliptin/metformin; gliclazide
Elevated*
1
Vildagliptin/metformin
Sitagliptin/metformin; gliclazide
Sitagliptin/metformin; gliclazide
PCI
Sitagliptin; metformin; glibenclamide
Sitagliptin; metformin
**
CABG
Vildagliptin/metformin; glimepiride
Elevated
1
Vildagliptin/metformin
Sitagliptin/metformin
Sitagliptin/metformin; gliclazide
PCI
1
****
1
Elevated
Vildagliptin/metformin; insulin
Sitagliptin; gliclazide
1
1
Sitagliptin; metformin; glibenclamide
Vildagliptin/metformin
Sitagliptin/metformin; gliclazide
80
Female
176
2.4
66
Male
25.3
0.9
LBBB
Sitagliptin/metformin
70
Male
147.8
1.1
Elevated
1
Sitagliptin/metformin; gliclazide
61
Male
45.1
0.9
Elevated
1
Sitagliptin/metformin; insulin
56
Male
144
1.0
Elevated
1
Vildagliptin/metformin; gliclazide
Vildagliptin/metformin; gliclazide
*Acute intra-stent thrombosis. **Severe aortic stenosis. ***Deceased. ****Thrombolysis.
LBBB = left bundle branch block; PCI = coronary percutaneous intervention; CABG = coronary artery bypass graft surgery; AMI = acute myocardial infarction; OAD = oral anti-diabetic drug.
Heart, Lung and Vessels. 2014, Vol. 6
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J.P.L. Nunes, et al.
184
patient died. Peak plasma levels for cardiac
troponin I varied in a relatively wide range,
from minor elevations under 1 ng/ml, to
values over 100 ng/ml (Table 2).
DISCUSSION
In the present study we describe a group of
35 diabetic patients with acute myocardial
infarction under current DPP-4 inhibitors
therapy. The vast majority of the patients
were also taking metformin. Myocardial
infarctions associated to the use of DPP-4
inhibitors have been shown to be very variable in terms of peak plasma cardiac troponin levels, the major parameter evaluated
in the present study. Mean peak plasma
troponin in myocardial infarctions associated to the use of DPP-4 inhibitors, however, was not significantly different from
the corresponding value in patients under
other forms of anti-diabetic therapy, the
same happening to myocardial infarctions
associated to the use of insulin, metformin
or sulfonylureas.
The treatment of type 2 diabetes mellitus
has been associated to modest results in
what concerns mortality and major cardiovascular disease, such as myocardial infarction and stroke. The clinical trials published in recent years, the Action to Control Cardiovascular Risk in Diabetes Study
(ACCORD), the Action in Diabetes and
Vascular Disease: Preterax and Diamicron
MR Controlled Evaluation (ADVANCE)
and the Veterans Affairs Diabetes Study
(VADT), all failed to show results of interest associated to intensive therapy, in what
concerns cardiovascular disease. ACCORD
has even shown an increased mortality
rate associated to intensive anti-diabetic
therapy. A meta-analysis (also including
data from the United Kingdom Prospective Diabetes [UKPDS] Study), however,
has shown that “intensive glucose control
reduced the risk for some cardiovascular
disease outcomes (such as nonfatal myocardial infarction), but did not reduce the
risk for cardiovascular death or all-cause
mortality, and increased the risk for severe
hypoglycemia” (9), findings essentially corroborated by a similar study (10).
The UKPDS 80 study did show favorable long-term effects of intensive therapy
(“legacy effect”), however the cohort under
study in UKPDS 80 was only a fraction of
the original UKPDS group of patients.
It has been speculated that “increases in
levels of insulin, not glucose, may be etiologic in cardio-vascular disease risk” (11),
and it has also been stated that “it can be
argued that lowering HbA1c is not, in and
by itself, a meaningful outcome” (12).
It is in this setting that new classes of antidiabetic drugs have been created, among
which the DPP-4 inhibitors have attracted
a considerable degree of interest. Promising laboratory data concerning DPP-4 inhibition have been published, including
improved endothelial function (13) and reduction of experimental infarct size in the
rat (14).
This group of drugs, which includes,
among others, sitagliptin, vildagliptin and
saxagliptin, are believed to act by inhibiting
the enzyme dipeptidyl peptidase 4, which
in turn degrades incretins such as GLP-1,
hormones released postprandially, thereby
increasing insulin and decreasing glucagon. DPP-4 inhibitors have been shown to
decrease glycated hemoglobin with a neutral effect on body weight and a low risk
for hypoglycemia (15). According to Jose
and Inzucchi, DPP-4 substrates are extensive, and “DPP-4 is not specific for GLP-1
and therefore has the potential to mediate a
wide range of pleiotropic effects (16).”
Two major clinical trials on DPP-4 inhibitors have been published. Saxagliptin was
compared to placebo in the Saxagliptin assessment of vascular outcomes recorded in
Heart, Lung and Vessels. 2014, Vol. 6
Myocardial infarction and DPP-4 inhibitors
patients with diabetes mellitus (SAVORTIMI 53) clinical trial (17). After a median
follow-up of 2.1 years, the study concluded
that “DPP-4 inhibition with saxagliptin did
not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased” (17).
In the Examination of cardiovascular outcomes with Alogliptin versus standard of
care (EXAMINE) clinical trial, a total of
5380 patients with acute coronary syndrome were randomized to take alogliptin
or placebo and followed for a median of 18
months (18). The authors concluded that
the rates of major adverse cardiovascular
events were not increased with alogliptin
as compared with placebo (18).
Meta-analyses and a pooled analysis (1921) failed to show an unfavorable cardiovascular profile for these drugs, however
in the comparator arm there were not only
data obtained with placebo but also with
active comparators, thereby limiting the
evaluation of DPP-4 inhibitors.
In the present study, the vast majority of
the patients with myocardial infarction associated to the use of DPP-4 inhibitors were
also taking metformin. Linear regression
analysis failed to indicate any significant influence on peak troponin I levels associated
to the presence of DPP-4 inhibitors. From a
theoretical standpoint, the presence of metformin could mask any possible effect of
DPP-4 inhibitors on the patho-physiology
of acute myocardial infarction. Peak plasma
troponin I values in the 31 patients treated
with metformin alone was 48.9±98.5 ng/
ml, a value which is very similar to the value for the 35 patients under DPP-4 therapy,
50.2±121.3 ng/ml. It is clearly difficult to
evaluate, using the present data, any possible effects of DPP-4 inhibitors, by themselves, on myocardial infarction.
We can reasonably suggest, however, that
DPP-4 inhibitors therapy doesn’t seem to
be associated to any increased importance
of acute myocardial infarction in patients
under metformin therapy, in what concerns peak plasma troponin I levels. In any
case, both vildagliptin/metformin and sitagliptin/metformin have become extremely
popular fixed drug associations, at least in
Portugal, where they represented the second and third absolute top-selling drugs in
the period January/March 2012 (22).
Study limitations – The present study has
significant limitations: it is a retrospective
study; indication bias is probably present,
in the sense that patients for whom doctors
chose different types of anti-diabetic therapy were probably different from each other;
for a considerable number of patients, it is
known that they were under oral anti-diabetic therapy but the exact nature of that
therapy is unknown; the duration of antidiabetic drug usage is also unknown; the
small dimension of the sample limits the
strength of conclusions; finally there are
many factors influencing troponin levels in
patients with myocardial infarction, reperfusion therapy being one of them (23).
CONCLUSION
In conclusion, we have described a group
of 35 diabetic patients with acute myocardial infarction under current anti-diabetic
therapy including a DPP-4 inhibitor. The
vast majority of the patients were also taking metformin.
We found no evidence that peak plasma
troponin I was different between patient
with acute myocardial infarction and use of
DPP-4i, when compared to cases not under
such therapy.
REFERENCES
1. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes,
other risk factors, and 12-yr cardiovascular mortality for
men screened in the Multiple Risk Factor Intervention
Trial. Diabetes Care. 1993; 16: 434-44.
2. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M.
Mortality from coronary heart disease in subjects with
Heart, Lung and Vessels. 2014, Vol. 6
185
J.P.L. Nunes, et al.
186
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. New Engl J Med. 1998;
339: 229-34.
Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, et al. Diabetes mellitus, fasting blood glucose
concentration, and risk of vascular disease: a collaborative
meta-analysis of 102 prospective studies. Lancet. 2010; 375:
2215-22.
Miranda VP, Rodrigues MJ, Goncalves FR, Nunes JPL. Effects of hypoglycemic agents on mortality and major cardiovascular outcomes in patients with type 2 diabetes mellitus:
a narrative review. Rev Port Cardiol 2009; 28: 1099-119.
Nissen SE, Wolski K. Effect of rosiglitazone on the risk
of myocardial infarction and death from cardiovascular
causes. N Engl J Med. 2007; 356: 2457-71.
Steen H, Giannitsis E, Futterer S, Merten C, Juenger C,
Katus HA. Cardiac troponin T at 96 hours after acute myocardial infarction correlates with infarct size and cardiac
function. J Am Coll Cardiol. 2006; 48: 2192-4.
American Diabetes Association. Standards of medical care
in diabetes-2012. Diabetes Care. 2012; 35 (Suppl. 1): S11-63.
Thygesen K, Alpert JS, White HD. Universal definition of
myocardial infarction. Eur Heart J. 2007; 28: 2525-38.
Kelly TN, Bazzano LA, Fonseca VA, Thethi TK, Reynolds
K, He J. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009;
151: 394-403.
Turnbull FM, Abraira C, Anderson RJ, Byington RP,
Chalmers JP, Duckworth WC, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009; 52: 2288-98.
Goodarzi MO, Psaty BM. Glucose lowering to control macrovascular disease in type 2 diabetes: treating the wrong
surrogate end point? JAMA 2008; 300: 2051-3.
Zannad F, Stough WG, Pocock SJ, Sleight P, Cushman WC,
Cleland JG, et al. Diabetes clinical trials: helped or hindered
by the current shift in regulatory requirements? Eur Heart
J. 2012; 33: 1049-57.
Matsubara J, Sugiyama S, Akiyama E, Iwashita S, Kurokawa H, Ohba K, et al. Dipeptidyl peptidase-4 inhibitor,
sitagliptin, improves endothelial dysfunction in association
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
with its anti-inflammatory effects in patients with coronary artery disease and uncontrolled diabetes. Circ J. 2013;
77: 1337-44.
Hausenloy DJ, Whittington HJ, Wynne AM, Begum SS,
Theodorou L, Riksen N, et al. Dipeptidyl peptidase-4 inhibitors and GLP-1 reduce myocardial infarct size in a glucosedependent manner. Cardiovasc Diabetol. 2013; 12: 154.
Karagiannis T, Paschos P, Paletas K, Matthews DR, Tsapas
A. Dipeptidyl peptidase-4 inhibitors for treatment of type
2 diabetes mellitus in the clinical setting: systematic review
and meta-analysis. BMJ. 2012; 344: 1369.
Jose T, Inzucchi SE. Cardiovascular effects of the DPP-4
inhibitors. Diab Vasc Dis Res. 2012; 9: 109-16.
Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson
J, Hirshberg B, et al. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus. N Engl J
Med. 2013; 369: 1317-26.
White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal
RM, Bakris GL, et al. Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes. N Engl J Med.
2013; 369: 1327-35.
Monami M, Dicembrini I, Martelli D, Mannucci E. Safety
of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin. 2011; 27 (Suppl. 3): 57-64.
Patil HR, Al Badarin FJ, Al Shami HA, Bhatti SK, Lavie
CJ, Bell DS, et al. Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes
mellitus. Am J Cardiol. 2012; 110: 826-33.
White WB, Pratley R, Fleck P, Munsaka M, Hisada M, Wilson C, et al. Cardiovascular safety of the dipetidyl peptidase-4 inhibitor alogliptin in type 2 diabetes mellitus. Diabetes Obes Metab. 2013; 15 668-73.
INFARMED. Analise do Mercado de Medicamentos em
Ambulatorio Março 2012. Lisbon, Portugal: Instituto da
Farmacia e Medicamento; 2012.
Katus HA, Remppis A, Scheffold T, Diederich KW, Kuebler W. Intracellular compartmentation of cardiac troponin
T and its release kinetics in patients with reperfused and
nonreperfused myocardial infarction. Am J Cardiol. 1991;
67: 1360-7.
Cite this article as: Nunes JPL, Rodrigues JD, Melão F. Acute myocardial infarction associated to DPP-4 inhibitors. Heart,
Lung and Vessels. 2014; 6(3): 180-186.
Source of Support: Nil. Disclosures: None declared.
Heart, Lung and Vessels. 2014, Vol. 6
ORIGINAL ARTICLE
Heart, Lung and Vessels. 2014; 6(3): 187-196
Agglutinins and cardiac surgery:
a web based survey of cardiac
anaesthetic practice; questions raised
and possible solutions
S. Shah1, H. Gilliland2, G. Benson3
1
Department of Anaesthesiology, Singapore General Hospital, Singapore; 2Cardiac Anaesthesia, Royal Victoria Hospital,
Belfast, UK; 3Haematology and Blood Transfusion Services, Royal Victoria Hospital, Belfast, UK
Heart, Lung and Vessels. 2014; 6(3): 187-196
ABSTRACT
Introduction: Cardiac surgery involves cardiopulmonary bypass during which the core temperature is generally lowered to hypothermic levels. Patients presenting for cardiac surgery are sometimes reported to have cold
or warm autoantibodies at the time of blood screening. It is known that cold agglutinins may cause potentially
life-threatening haemolysis, intracoronary haemagglutination leading to inadequate cardioplegia distribution,
thrombosis, embolism, ischaemia or infarction. The risk (if any) posed by warm autoantibodies is less clear.
Because of the absence of hospital policies and of clear UK guidelines that explain how to manage such cases, we
decided to conduct a web-based survey regarding standard anaesthesia practice in patients with both cold and
warm autoantibodies presenting for cardiac surgery.
Methods: We devised a short electronic survey asking for responses to 8 questions on cold auto-antibodies and
2 on warm auto-antibodies. This was sent to all members of the Association of Cardiothoracic Anaesthetists.
Responses were collated and expressed as percentages. Free text responses were analysed for trend or reported
verbatim.
Results: The results of our survey demonstrate that there is no consensus on the appropriate management of
such patients, with responses ranging from cancelling surgery to proceeding without additional precautions.
Conclusions: In collaboration with haematologists and taking into account the available evidence, our institution has now developed a management strategy for cardiac patients with cold autoantibodies. Further studies
will be required to determine the usefulness of our algorithm in daily practice.
Keywords: cardiac, surgery, cold, warm, auto-antibody.
INTRODUCTION
Cardiac surgery involves the use of cardiopulmonary bypass (CPB) during which
the core temperature is generally lowered
to hypothermic levels. For this reason, the
presence of cold agglutinins (CAs) is of
particular significance for cardiac surgical
patients. The main risk posed by CAs is of
Corresponding author:
Dr Shitalkumar Shah
MB BS, DNB, FCARCSI, MRCA
Singapore General Hospital,
Outram road, Singapore 169608
e-mail: [email protected]
potentially life-threatening haemolysis. In
addition, there is a risk of intracoronary
haemagglutination leading to inadequate
cardioplegia distribution, thrombosis, embolism, ischaemia or infarction (1-4).
In our institution (Royal Victoria Hospital,
Belfast, UK) cold agglutinins are not routinely tested preoperatively. Despite this,
the laboratory not infrequently reports the
presence of either CAs or “non-specific cold
autoantibodies” (NSCAs) on the pre-operative group and screen test. For the majority
of patients, this is a novel finding and there
are no pointers to clinical cold agglutinin
Heart, Lung and Vessels. 2014, Vol. 6
187
S. Shah, et al.
188
disease, such as acrocyanosis or laboratory
evidence of haemolytic anaemia. The cardiac anaesthesiologist is thus presented with
a problem: are these CAs or NSCAs likely
to be of clinical significance and, if so, what
steps should be taken to minimise the potential risk?
In the absence of any hospital policy, the
usual course of action in our institution has
been to solicit haematological advice. Sometimes further tests are requested, delaying
the proposed surgery, whilst on other occasions no specific action is prescribed. Adding to the general confusion, we have also
encountered a small number of patients
identified as having “warm” autoantibodies
or agglutinins (WAs) at the time of preoperative screening for cardiac surgery. Because
of the absence of any clear UK guidelines
that explain how to manage such cases, we
decided to conduct a web-based survey regarding standard anaesthesia practice in
patients, presenting for cardiac surgery,
with both cold and warm autoantibodies.
METHODS
We devised a short electronic survey consisting of 8 questions on CA/NSCAs and 2
questions on warm agglutinins in addition
to one question about the identity of the
responder’s institute. This national survey
was approved by the committee of the Association of Cardiothoracic Anaesthetists
(ACTA) and the survey questionnaire was
sent electronically to all ACTA members
over a 1 month period in July 2011.
The 8 questions related to CA/NSCAs and
the two relating to warm agglutinins are
shown in Table 1 below.
Responses were collated and the percentage
positive response to each question calculated. Where free text was permitted in an answer, comments were analysed to identify
trends or similarities. Where no trend ex-
isted, the response was reported verbatim.
Since the questionnaire asked about the
general experience of ACTA members, responses were assumed to reflect both adult
and paediatric practice.
RESULTS
We received a total of 40 completed questionnaires from 19 separate cardiac surgical institutes, 18 from the UK and 1 from
North America. 6 responders preferred not
to reveal name of their institution. The distribution of responses in shown in Table 2
below. These institutes carry either medium or high quantity work-load.
In response to question 1, most cardiac anaesthesiologists (87.5%) said they had heard
of cold agglutination syndrome, however,
10% stated that they had not. One responder declined to answer.
In response to our second question, 37 out
of 40 respondents (92.5%) had no protocol/
guideline in their institute. However, 3 responders from different institutes did have
an established policy in their place of work.
With regard to question 3, the majority of
anaesthetists (60%) reported that they encountered less than 5 cases of non-specific
cold autoantibodies per year in their practice. 27.5% said they never encountered
this problem, 7.5% said they encountered
between 5-10 cases per year and 2.5% stated that they experienced more than 10 cases each year in their practice.
For the next set of questions, options were
provided and multiple answers were allowed. Responding to question 4: 85% of
responders would refer a patient with cold
autoantibodies to a haematologist and 45%
said they would alter the conduct of cardiopulmonary bypass. 25% would also order
further investigations. By contrast, a small
number of responders (10%) stated that
they would not take any action if a patient
Heart, Lung and Vessels. 2014, Vol. 6
Agglutinins and cardiac surgery
189
Table 1 - Questionnaire.
Number
Question
1
Are you aware of cold agglutination syndrome Y/N
2
Are you aware of any protocol in your hospital for patients with non specific cold or warm
blood antibodies for cardiac surgery Y/N
3
How often in your cardiac practice do you encounter patient with non specific cold antibodies:
• >10 times per year
• 5-10 times per year
• <5 times per year
• never
4
What action do you take (in patients with cold autoantibodies). Tick any that apply:
• None
• Order further investigations
• Refer to haematologist
• Alter the conduct of cardiopulmonary bypass
• Other (please specify below)
5
If you order further investigations which of the following do they include. Tick any that apply:
• CBC and differential
• blood film
• antibody titre
• thermal amplitude
• liver function test
• coombs test
• other (please specify below)
6
Preoperatively, how would you manage raised cold antibody titres. Tick any that apply:
• No treatment
• steroids
• high dose IgG
• plasmapheresis
7
If you alter the conduct of CPB which of the following would you consider. Tick any that apply:
• Will not alter CPB conduct
• Off pump surgery
• Normothermia
• Warm blood cardioplegia
• Warm plus cold crystalloid cardioplegia
• Fibrillatory cross clamp
• Other
Do you consider myocardial temperature monitoring Y/N
8
If the proposed surgery necessitated deep hypothermic circulatory arrest, would you (single
answer):
• Proceed with additional precautions
• Proceed after informed consent (no additional precautions)
• Cancel the surgery
If you answered additional precautions please specify below
9
How often in your cardiac practice do you encounter patients with warm antibodies
10
What action do you take in patients with warm antibodies. Tick any that apply:
• Refer to haematologist
• Alter the conduct of CPB
• Order further investigations
• No action
Heart, Lung and Vessels. 2014, Vol. 6
S. Shah, et al.
190
Table 2 - Distribution of responses from UK hospitals .
Institution
No of
respondents
Freeman Hospital, Newcastle upon
Tyne, UK
4
Papworth, Papworth, UK
4
Guys and St Thomas, London, UK
3
Bristol Royal, Bristol, UK
3
Royal Victoria Hospital, Belfast, UK
2
Royal Infirmary of Edinburgh, Edinburgh, UK
2
John Radcliffe Hospital, Oxford, UK
2
The Royal Sussex County Hospital,
Brighton, UK
2
Royal Brompton Hospital, UK
2
GJNH, Glasgow, UK
1
Aberdeen Royal, Aberdeen, UK
1
The General Infirmary, Leeds, UK
1
James Cook University Hospital, UK
1
Hammersmith Hospital, London, UK
1
Barts and London, London, UK
1
Southampton University Hospital, UK
1
Wythenshaw Hospital, UK
1
Northern General hospital, Sheffield,
UK
1
Toronto General Hospital, Canada
1
Anonymous
6
were found to have cold autoantibodies preoperatively.
In response to question 5, when presented
with a list of options, more anaesthesiologists appeared willing to request further
investigations than the 25% who had stated
that they would do so in answer to question 4. Antibody titre was the most popular choice (35%), followed by thermal amplitude, blood film and Coomb’s test (each
27.5%). 12.5% responded that they would
order further investigations following the
haematologist’s advice.
One respondent stated that thermal amplitude testing was not available in their unit.
In answer to question 6, the most popular
choice was to refer the patient to a haematologist for preoperative management
(37.5%), 27.5% would consider preoperative plasmapheresis, 20% would give preoperative steroids, 12.5% would consider
high dose IgG and 7.5% said they would
decide whether or not to provide preoperative treatment based on thermal amplitude
results. A substantial number (30%) would
not offer any treatment preoperatively. For
the purposes of this question, we did not attempt to define “raised titres”.
Next, we explored how the conduct of cardiopulmonary bypass should be altered in
patients with high titre cold autoantibodies. The most popular option (70%) was to
conduct the surgery at normothermia with
60% opting to also give warm blood cardioplegia. 47.5% also considered off-pump
surgery (if feasible) and 20% would consider fibrillatory cross clamp as an option.
Only 10% would include myocardial temperature monitoring in their perioperative
strategy. 15% offered a free text answer
that ranged from “would consult haematologist”, “would perform literature review”
to “would cancel the surgery”.
Question 8 presented responders with a
difficult scenario. This time the options
offered were mutually exclusive and the
answers ranged from 10% who would proceed to deep hypothermic circulatory arrest without any additional precautions to
27.5% who would cancel the surgery altogether. The most popular option was to go
ahead with surgery but to take additional
precautions (42.5%). 20% declined to answer the question. When asked to comment
on the additional precautions to be taken,
most respondents would seek further advice
before proceeding. 15% would ask for hae-
Heart, Lung and Vessels. 2014, Vol. 6
Agglutinins and cardiac surgery
matology advice whereas 17.5% preferred a
multidisciplinary team approach. One respondent suggested conducting a literature
review. Only 2 respondents appeared happy
to devise a management plan without seeking further advice and both suggested using
plasmapheresis preoperatively.
Questions related to warm autoantibodies.
Question 9 revealed that this problem appeared to be less common with 45% saying
they never encountered it and another 40%
quoting an incidence of less than 5 times in
a year in their practice.
We then asked on the action to be taken,
five of those surveyed did not select any
of the options. Of the offered options, the
most popular was to talk to haematologists
(chosen by 70%), 25% volunteered to alter
the conduct of cardiopulmonary bypass
and 12.5% would order further investigations. 17.5% would not alter any aspect of
perioperative management.
DISCUSSION
This web-based survey demonstrates that
there is considerable confusion with regard to the correct management of cardiac
patients with cold or warm autoantibodies.
In terms of cold autoantibodies, the survey
shows that most cardiac anesthetists across
the UK have the same experience as us.
They see between 1 and 5 cases per year,
they have no policy in place as to what to do
with them, and the most popular and recurring option is to contact haematologists for
advice and to do whatever they instruct. In
terms of the actions taken, there is extreme
variability with some anaesthetists willing
to cancel surgery in any patient with CAs/
NSCAs and others prepared to go ahead
with deep hypothermia even in the face of
high antibody titres. Clearly, both cannot
be right. It is possible that some patients are
being placed at risk whilst others are hav-
ing life-saving surgery postponed unnecessarily.
With regard to warm autoantibodies, our
survey showed that some cardiac anaesthesiologists never encountered the problem
and that for some of those there was uncertainty about what to do next.
Warm autoantibodies, although responsible for the majority of autoimmune haemolytic anaemias (AIHAs), are active at
normal body temperature meaning that
cardiac surgery presents little in the way of
additional risk for these patients. There is
therefore no benefit in altering the conduct
of cardiopulmonary bypass. Nevertheless,
the finding of warm autoantibodies should
not simply be ignored. Prompt referral to a
haematologist for further investigation and
management is the appropriate course of
action as suggested by 70% of our respondents.
The remainder of this discussion will deal
with cold autoantibodies since these present the greater potential risk for the cardiac
surgical patient. Numerous case reports
have discussed the investigation and management of cardiac patients with cold autoantibodies, however there is as yet no consensus on the best plan of action. There is
an urgent need for institutional guidelines
on the perioperative management of cardiac
surgical patients with cold autoantibodies.
Cold autoantibodies in cardiac surgery. Typical CA’s are IgM autoantibodies that react
against I-antigens on the surface of erythrocytes. The cause of these CAs may be
primary/idiopathic, or more commonly,
secondary to an infective process (mycoplasma, infectious mononucleosis, other
viral infections) or a lymphoproliferative
disorder (5).
The broader term “cold autoantibodies” describes a spectrum of cold reactive proteins
ranging from the non-specific type, to the
typical IgM CA. The finding of a cold autoantibody on routine cross matching may
Heart, Lung and Vessels. 2014, Vol. 6
191
S. Shah, et al.
192
have a variety of implications depending
on titre and thermal amplitude. Titre represents the highest dilution of the serum
sample at which agglutination of red cells
in the cold is still seen: the higher the titre, the greater the likelihood of clinically
significant cold autoantibody activation.
Low titre cold autoantibodies (<1:40) can
be detected in virtually all normal subjects
under appropriate conditions and are clinically insignificant. (6). Higher levels of autoantibody may predispose the patient to
agglutination of blood in non-physiological
situations (e.g. during induced hypothermia) whilst, most rarely, cold agglutinins
can give rise to the cold agglutinin syndrome, a very rare type of autoimmune haemolytic anaemia (AIHA) with an estimated incidence of one case per million people
per year (7). Amongst the cardiac surgical
population the incidence of detectable cold
autoantibody has been stated to be approximately 0.8% to 4% (8).
Thermal amplitude is the temperature below which antibody activation occurs. Most
patients have no symptoms at normothermia, but those with high titre and high
thermal amplitude CAs can suffer haemagglutination at lower temperatures. If CAs
are active at temperatures which also permit complement fixation, haemolysis may
result. In the context of CPB, the initiation
of rewarming can lead to catastrophic haemolysis (5). Clues to the presence of intraoperative agglutination/haemolysis include
visible agglutination in the cardioplegia circuit, intracoronary thrombosis, inadequate
delivery of cardioplegia and high line pressures in the cardiopulmonary bypass circuit (2, 9). The consequence of this process
can be devastating with myocardial or cerebral infarction and multi-organ failure.
Much of what is known about cold agglutinins and their consequences during cardiac
surgery comes from case reports. Izzat et al.
(4) report a case where agglutination of red
blood cells occurred within a minute of initiation of antegrade cold blood cardioplegia
at 10oC leading to embolization in the coronary microcirculation. When the agglutinates were noticed, a coronary sinus cannula was inserted through the right atrium
and continuous retrograde cold crystalloid
cardioplegia was infused. Agglutinates
were noted to flush back from the coronary
arteries into the aortic root and the patient
did not show any signs of cardiac damage
postoperatively. This suggests that agglutination per se may be remediable if prompt
action is taken. Haemolysis on the other
hand may be much less amenable to intervention. An interesting case report by
Bracken et al (10) described cardiopulmonary bypass in a 67-year-old male patient
with cold agglutinins that had gone undetected prior to surgery. During surgery, the
red cells in the cardioplegia heat exchanger
clumped and the patient was noted to have
haemoglobinuria. On the evening of surgery, the patient developed a cold pulseless
left leg and underwent a bedside revascularization procedure. He died on the second
postoperative day of haemodynamic compromise. The authors commented that it is
not clear that cold agglutinins were directly
related to the terminal event.
In contrast to the numerous case reports, a
recent study by Barbara et al. (11) examined
the incidence and consequences of cold agglutinins in the cardiac surgical population over an 8-year period. They reported
only one case of haemolysis among 16 patients with either cold agglutinin disease
or detectable CAs between 2002 and 2010.
No serious harm resulted. Their findings
might lead one to conclude that the presence of CAs is of little clinical significance,
however it is worth noting that very few of
these patients were exposed to any degree
of hypothermia. In only one case was the
core temperature allowed to drift below
34oC and 14 out of 16 procedures deliber-
Heart, Lung and Vessels. 2014, Vol. 6
Agglutinins and cardiac surgery
ately employed warm blood cardioplegia.
The authors concluded that asymptomatic
CAs can safely be managed at normothermia without the need for further testing.
Nevertheless, some cardiac surgical procedures cannot be performed at normothermia, hence it is still important to be able to
determine which cardiac surgical patients
with CAs/NSCAs are at risk of agglutination/haemolysis during surgery.
Identification of patients at risk. The determination of risk is informed by both clinical history and laboratory tests.
Preoperative screening should include
queries about symptoms/signs of cold agglutination including acrocyanosis, haemoglobinuria, jaundice, and pallor (12). Laboratory tests for haemolytic anaemia should
also be used to determine whether or not
the patient has the clinical syndrome of
cold agglutination.
Given the non-physiological conditions
during cardiac surgery, patients without
preoperative symptoms or signs of haemolytic anaemia may still be at risk intraoperatively. In the absence of evidence of autoimmune haemolytic anaemia, the most
useful laboratory tests on which to base an
assessment of risk are thermal amplitude
and plasma titre (13).
These are difficult tests to perform, as accuracy necessitates that the blood sample
is maintained at 37°C until the serum has
been removed. A titre of around 1:10 is typical in normal individuals and up to 1:40
may regarded as clinically insignificant.
Haemolysis is rarely seen below titres of
1:1000 whilst individuals with the cold agglutinin syndrome typically have titres in
excess of 1:10,000 (6). Antibody titre varies with temperature. The presence of high
antibody titres at 4°C (1:10,000) and low
antibody titres at 37°C (1:16) is typical. Yet,
in some patients, antibody titres show a
flatter thermal spectrum with a moderately
high titre at 4°C (1:320) and a readily de-
monstrable titre at 37°C (1:64) (14). In the
typical profile of CA reactivity, profoundly
hypothermic temperatures cause intense
red cell agglutination, a process that reverses on rewarming. By contrast complement
fixation is a warm-reactive process. Hence,
complement-mediated haemolysis will only
occur if the spectrum of temperatures that
provoke agglutination overlaps that required for complement fixation.
To summarise, the spectrum of risk posed
by the presence of cold autoantibodies ranges from no risk at all to life-threatening red
cell agglutination/haemolysis. In terms of
cardiac surgery, the overall understanding
is that patients with low-titre (<1:32), lowthermal amplitude CAs (<20°C) are not at
particular risk of agglutination and may not
warrant any alteration in surgical plan (8).
Management. Management of patients deemed to be at risk of agglutination/haemolysis consists of preoperative strategies
to reduce antibody titre or reactivity and
intraoperative alterations to the conduct of
surgery.
Pre-operative strategies. Optimum pre-operative management for cardiac surgical patients with clinically significant CAs is still
unclear. Administration of steroids, azathioprine and cyclophosphamide has not been
shown to be of benefit (8).
There have been numerous reports of the
use of plasma exchange in patients with
CAs (2, 15-21). Plasma exchange is a complex procedure that must be performed at
normothermia and has several attendant
risks including that of infection and of creating large volume shifts, which may be
badly tolerated by cardiac patients. Since
most CA IgM is intravascular, up to 80%
of it may be removed by single 5-litre plasma exchange (22). Despite this, reports of
the effectiveness of plasma exchange in the
management of patients with CA have been
mixed, with some suggesting success (18)
while others have shown no benefit (20).
Heart, Lung and Vessels. 2014, Vol. 6
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S. Shah, et al.
194
IgG therapy is more costly but easier to administer than plasma exchange. A case report has shown that high-dose IgG administration just before cardiac surgery caused
an 8-fold reduction in the titre of CAs. The
mechanism of IgG’s action remains unclear.
The authors speculate that the high dose
IgG provides a protective coating over the
I-antigens on erythrocytes and in this way
prevents agglutination (23).
Intraoperative alterations in the conduct of
surgery. Several authors have reported successful outcomes from intraoperative measures taken to limit the haematologic and
cardiac consequences of cold exposure in
patients with CAs (24). The range of options for the intraoperative management of
these patients is wide (1, 2, 4, 8, 9, 25-37).
Reported strategies include:
- Warm blood cardioplegia: antegrade and/
or retrograde
- Warm ischaemic arrest
- Warm crystalloid cardioplegia to flush
coronaries followed by cold crystalloid
cardioplegia
Irrespective of the technique employed, it
is essential to limit systemic cooling during
CPB so as to maintain the systemic perfusion temperature above the thermal threshold of agglutinin activity. It is important not
to forget simple measures such as the use of
warming mattresses, heating of anaesthetic
gases intravenous fluids and blood products. Similarly, the operating room temperature should be elevated.
Management of intraoperative agglutination.
Cold agglutinins may not be detected prior
to surgery in some at risk patients (4, 9, 10,
26). First time detection of agglutination in
the intraoperative period warrants immediate action to raise the core temperature to
normothermia along with warm retrograde
myocardial washout as described above.
Further treatment should be directed towards ameliorating any resulting haemolysis or end-organ damage.
Further progress in our institution as a result
of this national survey. The results of our
survey were shared with colleagues in both
transfusion medicine and general haematology. We were able to explain the particular
risks posed by cardiac surgery whilst our
haematological colleagues could give advice
on how to establish the significance or nonsignificance of cold autoantibodies.
Working in collaboration with these experts, we developed local guidance (Royal
Victoria Hospital, Belfast, UK) on managing cardiac surgical patients with preoperative cold autoantibodies (Figure 1). Briefly,
the guidance recommends for all such patients to be investigated for symptoms/signs
of haemolytic anaemia. In common with
Barbara et al. (11), our guidance states that
those patients with evidence of haemolytic
anaemia must be referred to a haematologist for further management prior to surgery. Those patients without haemolytic
anaemia may follow two pathways depending on the type of surgery. If the surgery is
low-risk, it may be performed at modest hypothermia (34o C) with warm cardioplegia
and without further testing. Surgery where
significant hypothermia is necessary, or
highly likely, requires thermal amplitude
and titre testing preoperatively to determine the risk of agglutination/haemolysis.
The early involvement of haematologists is
essential in the perioperative management
of this latter group of patients.
CONCLUSION
Cold or warm autoantibodies may be detected for the first time on the preoperative
group and screen. Warm autoantibodies, although responsible for the majority of cases
of autoimmune haemolytic anaemia, present little in the way of additional risk for
cardiac surgical patients. Nevertheless, such
patients should be referred to a haematolo-
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Agglutinins and cardiac surgery
195
Figure 1 - Algorithm for the management of cardiac surgical patients with cold autoantibodies.
AIHA = autoimmune hemolytica; MCV = mean corpuscular volume; LDH = lactate dehydrogenase.
gist for further investigation and management of their haemolytic anaemia. By contrast, cardiac surgery may pose additional
risk for some patients with cold autoantibodies. Although many of these patients
have a very low likelihood of agglutination/
haemolysis if hypothermia is employed, the
management of patients with high titre,
high thermal amplitude cold autoantibodies
require meticulous planning before cardiac
operations.
The results of our survey demonstrate
that the appropriate management of such
patients remains unclear, with responses
ranging from cancelling surgery to proceeding without additional precautions.
Furthermore, the available literature yields
no clear consensus on either the degree of
risk posed by cooling or the antibody titre
that precipitates a need for alteration in the
conduct of surgery. Based on the results of
this study, extensive literate review and collaboration with colleagues in haematology,
we have developed and described a simple
management algorithm for dealing with
cardiac patients with cold autoantibodies.
Further studies will be necessary to confirm the use of our algorithm in everyday
practice.
REFERENCES
1. Shahian DM, Wallach SR, Bern MM. Open heart surgery
in patients with cold-reactive proteins. Surgical Clinics of
North America 1985; 65: 315-322.
2. Park JV, Weiss CI. Cardiopulmonary bypass and myocardial
protection: management problems in cardiac surgical patients with cold autoimmune disease. [Review]. Anesthesia
& Analgesia 1988; 67: 75-78.
3. Menasche P, Subayi JB, Piwnica A. Retrograde coronary sinus
cardioplegia for aortic valve operations: a clinical report on
500 patients. Annals of Thoracic Surgery 1990; 49: 556-563.
4. Izzat MB, Rajesh PB, Smith GH. Use of retrograde cold crystalloid cardioplegia in a patient with unexpected cold agglutination. Annals of Thoracic Surgery 1993; 56: 1395-1397.
5. Fischer GD, Claypoole V, Collard C. Increased pressures in
the retrograde blood cardioplegia line: an unusual presen-
Heart, Lung and Vessels. 2014, Vol. 6
S. Shah, et al.
196
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
tation of cold agglutinins during cardiopulmonary bypass.
Anesth Analg. 1997; 84: 454-6.
Rosse WF, Schrier SL, Mentzer WC, Landaw SA. Clinical
features and treatment of autoimmune haemolytic anaemia,
UpToDate, August 2013.
Berensten S, Ulvestad E, Langholm R, Beiske K, HjorthHansen H, Ghanima W, et al. Primary chronic cold agglutinin disease. Haematologica. 2006; 91: 460-460.
Agarwal SK, Ghosh PK, Gupta D. Cardiac surgery and coldreactive proteins. Annals of Thoracic Surgery. 1995; 60:
1143-50.
Dake SB, Johnston MFM, Brueggeman P, Barner HB. Detection of cold haemagglutination in blood cardioplegia
unit before systemic cooling of a patient with unsuspected
cold agglutinin disease. Annals of Thoracic Surgery 1989;
47: 914-15.
Bracken CA, Gurkowski MA, Naples JJ, Smith H, Steinmann A, Samuel J, et al. Case 6-1993. Cardiopulmonary bypass in two patients with previously undetected cold agglutinins. Journal of Cardiothoracic and Vascular Anesthesia
1993; 7: 743-749.
Barbara DW, Mauermann WJ, Neal JR, Abel MD, Schaff
HV, Winters JL. Cold agglutinins in patient undergoing cardiac surgery requiring cardiopulmonary bypass. Journal of
Thoracic and Cardiovascular Surgery 2013; 146: 668-80.
Hoffman JW, Gilbert TB, Hyder ML. Cold agglutinins complicating repair of aortic dissection using cardiopulmonary
bypass and hypothermic circulatory arrest: case report and
review. Perfusion 2002;17: 391-94.
Should we worry about cold reactive antibodies in cardiac
surgery? E-network forum, Californian Blood Bank Society.
Accessed 11 Feb 2013.
Packman CH, Leddy JP. Cryopathic hemolytic syndromes.
In: Williams WJ, Butler E, Ersley AJ, Lichtman MA, eds.
Hematolon. New York: McGraw Hill, 1990; 675-80.
Klein HG, Faltz LL, McIntosh CL, Appelbaum FR, Deisseroth AB, Holland PV. Surgical hypothermia in a patient
with a cold agglutinin. Management by plasma exchange.
Transfusion 1980; 20: 354-357.
Beebe DS, Bergen L, Palahniuk RJ. Anesthetic management
of a patient with severe cold agglutinin hemolytic anemia
utilizing forced air warming. Anesthesia & Analgesia 1993;
76: 1144-1146.
Zoppi M, Oppliger R, Althaus U, Nydegger U. Reduction of
plasma cold agglutinin titers by means of plasmapheresis to
prepare a patient for coronary bypass surgery. Infusionsther
Transfusionsmed. 1993; 20: 19-22.
Jewski C Jr, Gault E, Briggs M, Silberstein L. Benefit of a 37
degree C extracorporeal circuit in plasma exchange therapy
for selected cases with cold agglutinin disease. Journal of
Clinical Apheresis 1988; 4: 13-17.
Mastrogiovanni G, Masiello P, Iesu S, Senese I, Di Benedetto G. Management of cold agglutinemia with intermittent warm blood cardioplegia and normothermia. Annals of
Thoracic Surgery 1996; 62: 317.
Rodenhuis S, Maas A, Hazenberg CA, Das PC, Nieweg HO.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
Inefficacy of plasma exchange in cold agglutinin hemolytic
anemia-a case study. Vox Sang. 1985; 49: 20-25.
Shuma KH, Rock GA. Therapeutic plasma exchange. N
Engl J Med. 1984; 310: 762-771.
Powles R, Smith C, Kohn J, Hamilton Fairley G. Method of
removing abnormal protein rapidly from patients with malignant paraproteinaemias. Br Med J. 1971; 3: 664-7.
Kanemitsu S, Onoda K, Yamamoto K, Shimpo H. Simple
preoperative management for cold agglutinins before cardiac surgery. J Thorac Cardiovasc Surg. 2010; 140: 73-74.
Shulman IA, Petz LD. Red cell compatibility testing: Clinical significance and laboratory methods. In: Petz LD, Swisher SN, Kleinman S, Spence RK, Strauss RG, editors. Clinical Practice of Transfusion Medicine. New York: Churchill
Livingstone, 1996: 199-244.
Bedrosian CL, Simel DL. Cold hemagglutinin disease in the
operating room. South Med J. 1987; 80: 466-471.
Diaz JH, Cooper ES, Ochsner JL. Cardiac surgery in patients
with cold autoimmune diseases. Anesth Analg. 1984; 63:
349-352.
Holman WL, Smith SH, Edwards R, Huang ST. Agglutination of blood cardioplegia by cold-reacting autoantibodies.
Ann Thorac Surg. 1991; 51: 833-835.
Ko W, Isom OW. Cardiopulmonary bypass procedures in
patients with cold-reactive hemagglutination. A case report
and a literature review. J J Cardiovasc Surg (Torino). 1996;
37: 623-626.
Paccagnella A, Simini G, Nieri A, Da Col U, Frugoni C, Valfre C. Cardiopulmonary bypass and cold agglutinin. J Thorac Cardiovasc Surg. 1988; 95: 543.
Aoki A, Kay GL, Zubiate P, Ruggio J, Kay JH. Cardiac operation without hypothermia for the patient with cold agglutinin. Chest 1993; 104: 1627-1629.
Hearnsberger J, Ziomek S, Tobler G, Maxson T, VanDevanter S, Harrell JE, Jr. Management of cold agglutinemia with
warm heart surgical intervention: a case report. J Thorac
Cardiovasc Surg. 1993; 106: 756-757.
Lichtenstein SV, Salerno TA, Slutsky AS. Pro: warm continuous cardioplegia is preferable to intermittent hypothermic
cardioplegia for myocardial protection during cardiopulmonary bypass. J Cardiothorac Anesth. 1990; 4: 279-281.
Salerno TA, Houck JP, Barrozo CA, Panos A, Christakis GT,
Abel JG, et al. Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection. Ann Thorac
Surg. 1991; 51: 245-247.
Lichtenstein SV, Ashe KA, el Dalati H, Cusimano RJ, Panos
A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc
Surg. 1991; 101: 269-274.
Roe BB. Warm blood cardioplegia: back to square one. Ann
Thorac Surg. 1993; 55: 330-331.
Muehrcke DD, Torchiana DF. Warm heart surgery in patients with cold autoimmune disorders. Ann Thorac Surg.
1993; 55: 532-533.
Gokhale AG, Suhasini T, Saraswati V, Chandrasekhar N,
Rajagopal P. Cold agglutinins and warm heart surgery. J
Thorac Cardiovasc Surg. 1993; 105: 557.
Cite this article as: Shah S, Gilliland H, Benson G. Agglutinins and cardiac surgery: a web based survey of cardiac anaesthetic
practice; questions raised and possible solutions. Heart, Lung and Vessels. 2014; 6(3): 187-196.
Source of Support: Nil. Disclosures: None declared.
Acknowledgement: We would like to thank Dr Kathryn Maguire (Consultant Haematologist, Transfusion Services, Northern
Ireland Blood Transfusion Services) for her assistance in reviewing this paper and developing the management algorithm.
Heart, Lung and Vessels. 2014, Vol. 6
ORIGINAL ARTICLE
Heart, Lung and Vessels. 2014; 6(3): 197-203
Direct comparison between
cerebral oximetry by INVOSTM and
EQUANOXTM during cardiac surgery:
a pilot study
A. Pisano1, N. Galdieri1, T.P. Iovino1, M. Angelone1, A. Corcione2
1
Cardiac Anesthesia and Intensive Care Unit, “Monaldi” Hospital A.O.R.N. “Dei Colli”, Naples, Italy;
Anesthesia and Postoperative Intensive Care Unit, “Monaldi” Hospital A.O.R.N. “Dei Colli”, Naples, Italy
2
Heart, Lung and Vessels. 2014; 6(3): 197-203
ABSTRACT
Introduction: Several near-infrared spectroscopy oximeters are commercially available for clinical use, with
lack of standardization among them. Accordingly, cerebral oxygen saturation thresholds for hypoxia/ischemia
identified in studies conducted with INVOSTM models do not necessarily apply to other devices. In this study,
the measurements made with both INVOSTM and EQUANOXTM oximeters on the forehead of 10 patients during conventional cardiac surgery are directly compared, in order to evaluate the interchangeability of these two
devices in clinical practice.
Methods: Cerebral oxygen saturation measurements were collected from both INVOSTM 5100C and EQUANOXTM 7600 before anesthetic induction (baseline), two minutes after tracheal intubation, at cardiopulmonary
bypass onset/offset, at aortic cross-clamping/unclamping, at the end of surgery and whenever at least one of the
two devices measured a reduction in cerebral oxygen saturation equal to or greater than 20% of the baseline
value. Bland-Altman analysis was used to compare the bias and limits of agreement between the two devices.
Results: A total of 140 paired measurements were recorded. The mean bias between INVOSTM and EQUANOXTM was -5.1%, and limits of agreement were ±16.37%. Considering the values as percent of baseline, the
mean bias was -1.43% and limits of agreement were ±16.47. A proportional bias was observed for both absolute
values and changes from baseline.
Conclusions: INVOSTM and EQUANOXTM do not seem to be interchangeable in measuring both absolute values
and dynamic changes of cerebral oxygen saturation during cardiac surgery. Large investigations, with appropriate design, are needed in order to identify any device-specific threshold.
Keywords: near-infrared spectroscopy, cerebral oximetry, cardiac surgery.
INTRODUCTION
In recent years, near-infrared spectroscopy
(NIRS) is increasingly used to monitor regional cerebral oxygen saturation (rSO2)
during cardiac surgery (1-4). In fact, neurologic injury is still a common complication
Corresponding author:
Antonio Pisano, MD
Via Cupa della Torretta, 20
80070 Bacoli (NA), Italy
e-mail: [email protected]
after cardiac surgery, with rates of postoperative neurocognitive decline (PONCD) and
stroke of up to 50% and 1-3%, respectively
(5). Moreover, stroke after cardiac surgery
results in a 10-fold increase in mortality
and in a 3-fold increase in hospital stay (6).
In an attempt to reduce these potentially
disastrous complications, NIRS has been
therefore advocated as a routine monitor to
prevent or minimize brain injury by detecting cerebral oxygen supply-demand imbalances (7-9). Actually, several experimental
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A. Pisano, et al.
198
data are gradually accumulating to show
that both preoperative values and intraoperative changes of rSO2 can predict important complications and long-term outcomes
after cardiac surgery, including stroke (10),
delirium (11), neurocognitive decline (12),
organ dysfunction (13, 14), length of hospital stay (12, 13, 15) and mortality (14).
Nevertheless, not everyone considers these
evidences sufficient to justify the routine
use of NIRS monitoring in cardiac surgery
(4, 16), that remains debated (7, 17) and
poorly defined, with little consensus for
its appropriate use (3). Probably, one of
the reasons for this is the poor agreement
among different devices (3, 7, 17-19), that
has been also confirmed by two recent investigations (2, 20).
Currently, several NIRS devices are commercially available for clinical use, with
lack of standardization among them (2, 16,
19, 21). In fact, although the various models are mostly based on spatial resolution
spectroscopy (16, 22), they differ in numerous important aspects related to the acquisition of their cerebral oxygen saturation
measurements, including the algorithms
adopted, the type of light source, the wavelengths of light emitted and the distance
between the various light emitters and detectors (19). This makes comparisons between clinical studies using different devices difficult and, therefore, rSO2 thresholds
for the development of hypoxia/ischemia
remain elusive (23, 24). Particularly, since
the majority of clinical data currently available have been generated using various INVOSTM devices (the first to be approved by
the U.S.A. Food and Drug Administration)
(16), it is not clear whether the thresholds
identified in studies conducted with these
models (11, 12-14, 25) may also apply to devices from other companies.
In the present study, for the first time far as
the authors know, the measurements made
by both INVOSTM and EQUANOXTM NIRS
oximeters on the forehead of adult patients
during different moments of cardiac surgical procedures are directly compared, with
the objectives of evaluating both the feasibility of such simultaneous measurements
and the interchangeability of the two devices in clinical practice.
METHODS
The study protocol was approved by the local Ethical Committee. After informed consent, 10 patients (6 males, 4 females), mean
age 65.1 ± 15.84, scheduled for conventional cardiac surgery with or without cardiopulmonary bypass (CPB) were enrolled
in the study (Table 1).
Two different NIRS monitors were applied
to patients: the 2-wavelength INVOSTM
5100C (Somanetics, Troy, MI) and the
3-wavelength EQUANOXTM 7600 (Nonin
Medical, Inc, Plymouth, MN).
After rubbing and cleaning the skin with
an alcohol swab, 2 sensors (one left and
one right) Adult SomaSensor SAFB-SM
(Covidien, Mansfield, MA) and 2 sensors
(one left and one right) EQUANOXTM ADVANCETM Sensor-Adult model 8004 CA
(Nonin Medical, Inc, Plymouth, MN) were
placed over the forehead of the patients, as
close as possible, being careful not to overlap light emitters and detectors. INVOSTM
sensors were placed lower than EQUANOXTM ones in five patients, and higher than
EQUANOXTM ones in the other five (Figure 1). All sensors where then connected to
the respective devices via their proprietary
cables.
Regional cerebral oxygen saturation (rSO2)
measurements were collected before anesthetic induction with patients breathing
ambient air (baseline values), two minutes
after tracheal intubation, two minutes after
CPB onset, at aortic cross-clamping, at aortic unclamping, at CPB offset (when appli-
Heart, Lung and Vessels. 2014, Vol. 6
Direct comparison between INVOSTM and EQUANOXTM in cardiac surgery
Table 1 - Age, sex, type of surgery, number of measurements recorded (from each device) and number of desaturations ≥20% from baseline (displayed by one or both of the two devices) of the patients investigated.
Patient
N.
Sex
Age
(years)
Type
of surgery
N. of
N. of desaturations ≥20% from baseline
measurements
INVOSTM EQUANOXTM
Both
(L+R)
1
M
63
AVR
14
0
0
0
2
M
60
CABG
20
5
3
3
3
F
79
OPCAB
12
5
0
0
4
M
79
MVR+ CABG
20
6
0
0
5
M
75
CABG
14
0
0
0
6
M
44
AVR
14
0
0
0
7
M
75
MVR
14
0
0
0
8
F
70
OPCAB
6
0
0
0
9
F
74
OPCAB
12
4
0
0
10
F
32
MVR
14
0
0
0
M = male; F = female; L = left; R = right; AVR = aortic valve replacement; CABG = coronary artery bypass graft; OPCAB =
off-pump coronary artery bypass; MVR = mitral valve replacement.
cable), at the end of surgery and whenever
at least one of the two devices measured a
bilateral or monolateral reduction in cerebral oxygen saturation equal to or greater
than 20% of the baseline value. Each measurement, as well as an absolute value, was
also recorded as a percentage of the respective baseline value according to the formula:
% of baseline=absolute valuex100/baseline
value.
In all patients, whilst the EQUANOXTM
monitor seemed not significantly influenced by the presence of the operating
INVOSTM sensors, no rSO2 values were
displayed (and a “poor signal quality” error message appeared) on the INVOSTM
Figure 1 - Relative positioning of NIRS sensors on the forehead of patients 1, 3, 5, 7 and 9 (panel A) and
2, 4, 6, 8 and 10 (panel B). NIRS = near-infrared spectroscopy.
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A. Pisano, et al.
200
oximeter when the EQUANOXTM device
was switched on. For this reason, it was
not possible to record the rSO2 values from
the two devices simultaneously. Therefore,
immediately after collecting INVOSTM data,
it was turned off and, simultaneously, the
EQUANOXTM device was turned on and its
data were recorded.
Bland-Altman analysis was used to compare the bias and limits of agreement (bias
± standard deviation x 1.96) between the
two devices. Moreover, linear regression
was applied to the Bland-Altman plots
in order to test the presence of a proportional bias. IBM SPSS Statistics software v
19.0 (IBM, Armonk, New York) was used
for statistical analysis. A 2-tailed value of
p<0.05 was considered significant.
RESULTS
A total of 140 measurements (70 left, 70
right) were collected from both devices
in the 10 patients (Table 1). The mean
bias between INVOSTM and EQUANOXTM
was -5.1%, and limits of agreement were
±16.37%. (Figure 2A) The Bland-Altman
plot showed the presence of a statistically significant proportional bias (n=140;
R=0.541; R2=0.293; p=0.000).
When considering the dynamic changes
of rSO2 (expressed as percent of baseline)
showed by the two devices (120 measurements), the mean bias was -1.43% and
limits of agreement were ±16.47 (Figure
2B). Also in this case, there was a significant proportional bias (n=120; R=0.680;
R2=0.462; p = 0.000).
Interestingly, of the 20 total episodes (considering each individual sensor) of significant (or “threshold”) cerebral desaturation
(i.e., a reduction equal to or greater than
20% from baseline) (25, 26) reported by
INVOSTM in four patients, mostly during
heart displacement for coronary artery exposure or during episodes of hypotension
over CPB, only 3 (in one patient) were
also reported by EQUANOXTM. No other
“threshold” desaturation was reported by
EQUANOXTM (Table 1).
All significant desaturations were prompt-
Figure 2 - Bland-Altman analysis between absolute values (panel A) and changes from baseline (panel
B) of rSO2 measured by INVOSTM and EQUANOXTM in the 10 patients.
Heart, Lung and Vessels. 2014, Vol. 6
Direct comparison between INVOSTM and EQUANOXTM in cardiac surgery
ly corrected with conventional strategies
(such as administer fluids or vasopressors
or raise pump flow) (13) and no patients
had complications.
DISCUSSION
The results of this investigation suggest a
clinically important difference between INVOSTM and EQUANOXTM in measuring cerebral oxygen saturation as well as its variations during cardiac surgery, probably due
to some of the characteristics in which they
differ (such as the number of light emitters
and detectors, the different distance between them and, consequently, a different
tissue penetration of light, the number of
wavelengths adopted, and a different builtin proprietary algorithm to assess oxygen
saturation) (20).
In particular, in our series the bias between
INVOSTM and EQUANOXTM in measuring
absolute values of rSO2 showed a moderate correlation with the mean values from
the two devices, with a tendency of INVOSTM to underestimation (or a tendency
of EQUANOXTM to overestimation) for the
lower values. Of course, it is rather difficult
to determine which of the two devices provide the “more true” absolute values.
Most importantly, the limits of agreement
were very wide. Accordingly, the two devices do not seem to be interchangeable in
routine clinical practice. Therefore, the results of previous investigations that identified threshold absolute values of rSO2 able
to predict outcomes such as postoperative
delirium (11) and mortality (14) using INVOSTM may not to be applicable to EQUANOXTM.
While these results are not particularly surprising, given that a poor reliability of absolute values of rSO2 measured by INVOSTM
had already been showed (27, 28), the similar differences observed also in changes
from baseline given by the two devices require caution in interpreting trends given
by EQUANOXTM according to thresholds
previously identified in studies using INVOSTM (1, 12-14, 25, 26). In fact, although
the mean inter-device bias for dynamic
changes of rSO2 was lower than that for
the absolute values, the limits of agreement
were, also in this case, wide. Moreover, an
even stronger proportional bias was observed, meaning that the two devices may
display a different magnitude of desaturation in similar clinical situations. Accordingly, we observed much more “threshold”
desaturations from INVOSTM than from
EQUANOXTM, although the number of episodes is not sufficient for confident statistical analysis.
Of course, these results do not exclude
that both devices may adequately describe
the variations in cerebral oxygen supplydemand balance, although device-specific
thresholds are probably needed to interpret
correctly these variations in clinical practice.
Our findings are consistent with the results
of other recent investigations. In fact, even
if this is the first report of a direct comparison between INVOSTM and EQUANOXTM
measurements at cerebral level and in a
clinical context, the agreement between
the two devices has been previously evaluated, both directly (2, 20) and indirectly
(2, 19, 29), in healthy volunteers. Davie et
al. (19) reported variable sensitivity to extracranial tissue contamination among INVOSTM, EQUANOXTM, and FORE-SIGHT®
(CAS Medical Systems, Inc, Brandford, CT)
devices. This may partly explain the interdevice differences in absolute values of
rSO2, but should not significantly affect the
variations from baseline. However, Fellahi
et al. (20) and Hyttel-Sorensen et al. (29)
demonstrated that INVOSTM and EQUANOXTM, positioned simultaneously on calves
or one at the time on forearms of healthy
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A. Pisano, et al.
202
volunteers, respectively, are not comparable in measuring both absolute values and
dynamic changes of peripheral rSO2 after
vascular occlusion tests. Finally, Bickler
et al. (2) evaluated the performance of five
commercially available cerebral oximeters
(including INVOSTM and EQUANOXTM),
applied two at the time per subject in 23
adult healthy volunteers, and found a large
variation in reading bias (calculated as the
difference between the instrument’s reading with the weighted saturation of venous
and arterial blood) between subjects, especially during hypoxia. Similar differences
were also found when comparing INVOSTM
with other devices (18, 30).
This study has several limitations, the
most important being the small number
of patients enrolled. However, the number
of paired measurements, that can be considered independent among themselves,
allows us to give some significance to our
findings. One of the reasons why we limited our observations to a few patients is the
convinction, gained during the collection
of these initial data, that different study
designs may be preferable in order to investigate the differences among the various
devices. In fact, direct comparison of two
NIRS devices seems to be somewhat difficult, since the sampled areas, though close,
are not the same and interferences between
the two sensors can not be excluded (20,
30). Regarding the latter, we report for the
first time an important interference, due to
which the paired measurements were not
simultaneous but spaced each other by a
few seconds, that is another important limitation of the present study. Maybe, in other
investigations not reporting such interference, the distances between sensors were
greater: in fact, Fellahi et al. (20) placed the
sensors on calves, while Bickler et al. (2)
applied only two sensors (one for each device) on the forehead, instead of four as in
this report. A plausible explanation for IN-
VOSTM but not EQUANOXTM being markedly disturbed by the other device is the
use of three wavelengths (730, 810 and 880
nm) by EQUANOXTM and two wavelengths
by INVOSTM, in particular two of the three
used by EQUANOXTM (730 and 810 nm).
CONCLUSION
The present study suggests that INVOSTM
and EQUANOXTM are not interchangeable
in measuring both absolute values and dynamic changes of cerebral rSO2 during cardiac surgery. Accordingly, device-specific
thresholds are probably needed to guide
interventions aimed to prevent postoperative brain injury as well as other adverse
outcomes. Since direct comparison of NIRS
devices in such clinical context seems to be
of poor feasibility and difficult interpretation, large investigations on each device are
needed in order to identify any of such specific thresholds and to allow a more extensive and better-defined use of this promising technology.
REFERENCES
1. Deschamps A, Lambert J, Couture P, Rochon A, Lebon JS,
Ayoub C, et al. Reversal of decreases in cerebral saturation
in high-risk cardiac surgery. J Cardiothorac Vasc Anesth
2013; 27: 1260-6.
2. Bickler PE, Feiner JR, Rollins MD. Factors affecting the
performance of 5 cerebral oximeters during hypoxia in
healthy volunteers. Anesth Analg 2013; 117: 813-23.
3. Zacharias DG, Lilly K, Shaw CL, Pirundini P, Rizzo RJ,
Body SC, et al. Survey of the clinical assessment and utility of near-infrared cerebral oximetry in cardiac surgery. J
Cardiothorac Vasc Anesth. 2014; 28: 308-16.
4. Zheng F, Sheinberg R, Yee MS, Ono M, Zheng Y, Hogue
CW. Cerebral near-infrared spectroscopy monitoring and
neurologic outcomes in adult cardiac surgery patients: a
systematic review. Anesth Analg 2013; 116: 663-76.
5. Newman M, Mathew J, Grocott H, Mackensen GB, Monk
T, Welsh-Bohmer KA, et al. Central nervous system injury
associated with cardiac surgery. Lancet 2006;368:694-703.
6. Gottesman RF, Sherman PM, Grega MA, Yousem DM,
Borowicz LM Jr, Selnes OA, et al. Watershed strokes after
cardiac surgery: Diagnosis, etiology, and outcome. Stroke
2006; 37: 2306-11.
7. Vernick WJ, Gutsche JT. Pro: cerebral oximetry should be
a routine monitor during cardiac surgery. J Cardiothorac
Vasc Anesth 2013; 27: 385-9.
Heart, Lung and Vessels. 2014, Vol. 6
Direct comparison between INVOSTM and EQUANOXTM in cardiac surgery
8. Fischer GW. Recent advances in application of cerebral oximetry in adult cardiovascular surgery. Semin Cardiothorac
Vasc Anesth 2008; 12: 60-9.
9. Fedorow C, Grocott HP. Cerebral monitoring to optimize
outcomes after cardiac surgery. Curr Opin Anaesthesiol
2010; 23: 89-94.
10. Goldman S, Sutter F, Ferdinand F, Trace C. Optimizing
intraoperative cerebral oxygen delivery using noninvasive cerebral oximetry decreases the incidence of stroke
for cardiac surgical patients. Heart Surg Forum. 2004; 7:
E376-81.
11. Schoen J, Meyerrose J, Paarmann H, Heringlake M, Hueppe
M, Berger KU. Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump
cardiac surgery patients: a prospective observational trial.
Crit Care 2011; 15: 218.
12. Slater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown
JM 3rd, et al. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery.
Ann Thorac Surg 2009; 87:36-44.
13. Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge
D, Iglesias I, et al. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective
study. Anesth Analg. 2007; 104: 51-8.
14. Heringlake M, Garbers C, Käbler JH, Anderson I, Heinze
H, Schön J, et al. Preoperative cerebral oxygen saturation
and clinical outcomes in cardiac surgery. Anesthesiology.
2011; 114: 58-69.
15. Apostolidou I, Morrissette G, Sarwar MF, Konia MR,
Kshettry VR, Wahr JA, et al. Cerebral oximetry during cardiac surgery: the association between cerebral oxygen saturation and perioperative patient variables. J Cardiothorac
Vasc Anesth. 2012; 26: 1015-21.
16. Ghosh A, Elwell C, Smith M. Review article: cerebral nearinfrared spectroscopy in adults: a work in progress. Anesth
Analg 2012; 115: 1373-83.
17. Gregory A, Kohl BA. Con: near-infrared spectroscopy has
not proven its clinical utility as a standard monitor in cardiac surgery. J Cardiothorac Vasc Anesth 2013; 27: 390-4.
18. Dullenkopf A, Frey B, Baenziger O, Gerber A, Weiss M.
Measurement of cerebral oxygenation state in anaesthetized children using the INVOS 5100 cerebral oximeter.
Paediatr Anaesth 2003; 13: 384-91.
19. Davie SN, Grocott HP. Impact of extracranial contamination on regional cerebral oxygen saturation: A comparison
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
of three cerebral oximetry technologies. Anesthesiology
2012; 116: 834 -40.
Fellahi JL, Butin G, Fischer MO, Zamparini G, Gérard JL,
Hanouz JL. Dynamic evaluation of near-infrared peripheral oximetry in healthy volunteers: a comparison between
INVOS and EQUANOX. J Crit Care 2013; 28: 881.
Highton D, Elwell C, Smith M. Noninvasive cerebral oximetry: is there light at the end of the tunnel? Curr Opin
Anaesthesiol 2010; 23: 576-81.
Murkin JM, Arango M. Near-infrared spectroscopy as an
index of brain and tissue oxygenation. Br J Anaesth 2009;
103: (Suppl. 1): 3-13.
Smith M, Elwell C. Near-infrared spectroscopy: shedding
light on the injured brain. Anesth Analg 2009; 108: 105557.
Smith M. Shedding light on the adult brain: a review of the
clinical applications of near-infrared spectroscopy. Philos
Trans A Math Phys Eng Sci. 2011;369:4452-69.
Denault A, Deschamps A, Murkin JM. A proposed algorithm for the intraoperative use of cerebral near-infrared
spectroscopy. Semin Cardiothorac Vasc Anesth. 2007; 11:
274-81.
Samra SK, Dy EA, Welch K, Dorje P, Zelenock GB, Stanley
JC. Evaluation of a cerebral oximeter as a monitor of cerebral ischemia during carotid endarterectomy. Anesthesiology. 2000; 93: 964-70.
Dullenkopf A, Baulig W, Weiss M, Schmid ER. Cerebral
near-infrared spectroscopy in adult patients after cardiac
surgery is not useful for monitoring absolute values but
may reflect trends in venous oxygenation under clinical
conditions. J Cardiothorac Vasc Anesth. 2007; 21: 535-9.
Leyvi G, Bello R, Wasnick JD, Plestis K. Assessment of
cerebral oxygen balance during deep hypothermic circulatory arrest by continuous jugular bulb venous saturation
and near-infrared spectroscopyJ Cardiothorac Vasc Anesth.
2006; 20: 826-33.
Hyttel-Sorensen S, Hessel TW, Greisen G. Peripheral tissue
oximetry: comparing three commercial near-infrared spectroscopy oximeters on the forearm J Clin Monit Comput.
2014; 28: 149-55.
Moerman A, Vandenplas G, Bové T, Wouters PF, De Hert
SG. Relation between mixed venous oxygen saturation and
cerebral oxygen saturation measured by absolute and relative near-infrared spectroscopy during off-pump coronary
artery bypass grafting. Br J Anaesth 2013; 110: 258-65.
Cite this article as: Pisano A, Galdieri N, Iovino TP, Angelone M, Corcione A. Direct comparison between cerebral oximetry
by INVOSTM and EQUANOXTM during cardiac surgery: a pilot study. Heart, Lung and Vessels. 2014; 6(3): 197-203.
Source of Support: Nil. Disclosures: Dr. Galdieri and Dr. Pisano have lectured in a course entitled “INVOS monitoring in
cardiac and vascular surgery”. Dr. Galdieri received a grant from Covidien for this.
Heart, Lung and Vessels. 2014, Vol. 6
203
CASE REPORT
Heart, Lung and Vessels. 2014; 6(3): 204-207
204
Life threatening tension
pneumothorax during cardiac surgery.
A case report
A. Jain, D. Arora, R. Juneja, Y. Mehta, N. Trehan
Medanta Institute of Critical Care and Anesthesiology, Medanta The Medicity, Gurgaon, Haryana
Heart, Lung and Vessels. 2014; 6(3): 204-207
ABSTRACT
Tension pneumothorax is a life threatening condition that occurs when the intrapleural pressure exceeds atmospheric pressure. It requires prompt diagnosis and immediate treatment. Tension pneumothorax developing
postoperatively after cardiac surgery is not uncommon but occurrence in the operating room during cardiac
surgery is rare. We report a case of tension pneumothorax intraoperatively during off pump coronary artery
bypass grafting.
Keywords: pneumothorax, cardiac surgery, hypotension.
INTRODUCTION
CASE REPORT
Tension pneumothorax occurs due to a one
way communication between lung parenchyma and the pleural cavity leading to air
entrapment in the pleural cavity with each
inspiration with inability to release it during expiration. It requires prompt diagnosis
and immediate treatment or it may lead to
respiratory failure and cardiovascular collapse (1, 2). Tension pneumothorax developing postoperatively after cardiac surgery
is not uncommon but occurrence intraoperatively during cardiac surgery is rare and
not yet reported in the English literature.
We report a case of tension pneumothorax
occurring intraoperatively during off pump
coronary artery bypass grafting (OPCAB).
A 62 years, 60 kg male with coronary artery
disease, past history of smoking (60 packyears), history of dyspnoea and chest pain on
exertion NYHA grade II-III since one year
was electively admitted for OPCAB. There
was no history of chronic cough, recurrent
respiratory tract infections, previous hospitalization, use of beta2 agonist or steroids,
or history suggestive of chronic obstructive
pulmonary disease (COPD), occupational
lung disease or tuberculosis. General physical and systemic examination was within
normal limits. Preoperative haematological
investigations and pulmonary function test
(PFT) were within normal limits. Chest radiograph revealed emphysematous changes.
Transthoracic echocardiography showed no
regional wall motion abnormality (RWMA)
with normal valvular and left ventricular
(LV) function.
Induction of general anesthesia was un-
Corresponding author:
Dr. Ashish Jain
DNB Anesthesia
Medanta- The Medicity
Sector 38, Gurgaon, Haryana, INDIA
e-mail: [email protected]
Heart, Lung and Vessels. 2014, Vol. 6
Tension pneumothorax during cardiac surgery
eventful and anesthesia was induced with
fentanyl sulphate, midazolam, thiopentone
sodium and maintained with isoflurane and
air oxygen mixture. Orotracheal intubation
was easy, facilitated with vecuronium bromide and without airway trauma. Intermittent vecuronium bromide and fentanyl sulphate were used intravenously in standard
doses. Pulmonary artery catheter introducer sheath and a triple lumen central venous
catheter were inserted in the right internal
jugular vein under ultrasound guidance
in the first attempt without any complication. A pulmonary artery catheter was then
floated through the sheath. During OPCAB
the left pleura was opened whilst harvesting the left internal mammary artery while
the right pleura remained intact. The left
lung was observed to be hyperinflated without any evidence of bullae. The patient was
mechanically ventilated on volume control
ventilation mode under low flow anesthesia at 1.0 litre/minute with a tidal volume
(TV) of 8 ml/kg, respiratory rate of 14/min
and I:E ratio of 1:2.5 without application of
PEEP, achieving a peak inspiratory pressure
(PIP) of 18 cm of H2O. During coronary artery grafting the tidal volume was decreased
to 5 ml/kg and respiratory rate increased to
20/min because the left lung was obscuring the surgical field. Post induction arterial
blood gas analysis (ABG) showed PaO2 of
80 mm Hg on FiO2 of 0.6 with rest of the
values in normal range. Intraoperative endotracheal suctioning revealed excessive
tracheobronchial secretions, simultaneously FiO2 was raised to 1.0 and subsequent
ABG remained within normal limits.
Major parts of the procedure remained uneventful. However at the time of grafting of
proximal ends of saphenous vein to the aorta we observed a partial collapse of the left
lung and the ventilator bellows not inflating fully. This raised a suspicion of a leak
in the breathing circuit but we did not find
any circuit leak. An attempt was made to
auscultate the chest but was not successful
because the patient was draped with sterile
towels. The anesthesia machine was crosschecked by a biomedical engineer but no
technical error was detected. The inspiratory gas flow was increased to 3.0 liter/minute resulting in adequate expansion of the
left lung, restoration of tidal volume and
full inflation of ventilator bellows. Bulging
of right side pleura was not observed on inspiration.
During chest closure the heart rate (HR) increased to 130 beats/min with decrease in
arterial blood pressure (ABP) to 80/60 mm
Hg without any significant change in PIP,
pulmonary artery pressure (PAP), 22/14
mm Hg and central venous pressure (CVP),
9 mm Hg. It was thought that the hemodynamic instability was due to the effect of
chest closure and therefore was managed
by administering fluid boluses and titrated
increase in the dose of norepinephrine and
epinephrine.
At the end of the procedure, when all drapes
were removed and dressing had been applied on the surgical wound while the patient was still on mechanical ventilation,
there was an increase in PIP to 40 cm H2O.
This was immediately followed by increase
in HR to 150/min and a decrease in ABP
to 60/40 mm Hg. We attempted to manage
this episode as the previous one and transesophageal echocardiography (TEE) was
called for. However there was no response
to intravenous fluids and high doses of vasopressors. An increase in CVP to 14 mm Hg
and PAP to 28/20 mm Hg with a decrease
in cardiac index (CI) and cardiac output
(CO) were observed. Auscultation of the
chest revealed decreased breath sounds on
the right side of the chest and crepitus was
palpable over the neck and chest. This led
to suspicion of subcutaneous emphysema
and a diagnosis of tension pneumothorax
was made. Immediately tube thoracostomy
was performed on the right side and a gush
Heart, Lung and Vessels. 2014, Vol. 6
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A. Jain, et al.
206
of air bubbles were observed in the under
water seal drainage system followed by normalization of heart rate, blood pressure and
pulmonary artery pressure. TEE performed
subsequently to rule out any signs of myocardial ischemia revealed normal LV function, adequately filled LV, no RWMA and
no valvular regurgitation.
The patient was then shifted to the postoperative intensive care unit and a chest radiograph obtained which revealed full lung
expansion and mild subcutaneous emphysema. The trachea was extubated on the
first postoperative day, chest tubes were removed on the third postoperative day without any evidence of pneumothorax on chest
radiograph. Rest of the postoperative period was uneventful and the patient was discharged on the seventh postoperative day.
DISCUSSION
Tension pneumothorax is a life threatening condition and its occurrence intraoperatively should be promptly diagnosed and
treated (3, 4). The most common causes are
regional blocks (40% of reported cases),
airway instrumentation (19%), barotrauma (16%), and placement of central venous
lines (7%) (5). Patients with COPD are at
increased risk (3). In our patient the cause
of tension pneumothorax was thought
to be rupture of an emphysematous bulla
that might have been present on the right
lung particularly since the chest radiograph
showed emphysematous changes despite
normal PFT. Moreover the patient was a
chronic smoker and during surgery the
lungs were observed to be hyperinflated.
A communication between lung parenchyma and pleural space may act as a one way
valve allowing air to enter inside the pleural cavity during inspiration but preventing the air from escaping naturally during
expiration. This results in an expanding
pneumothorax that forces the lungs to collapse, increases intrathoracic pressure that
causes decrease in venous return to the
heart, decrease in stroke volume, cardiac
output, cardiac index, blood pressure and
tachycardia eventually leading to hemodynamic compromise (6). McLoud et al. (7)
reported a rise in PADP consistent with the
development of pneumothorax in 3 patients
(2 on mechanical ventilation). Yu and Lee
(8) reported an increase only in PADP
with pneumothorax and they considered
it could be due to the transmission of the
intrapleural pressure to the pulmonary vasculature. Connolly (9) reported the first and
only description of a patient with tension
pneumothorax in whom all hemodynamic
and ABG parameters were measured. The
authors described the onset of hypoxemia,
acidosis, increased CVP, PAP and decrease
of CO, consistent with the development of
pneumothorax.
Standard medical reference texts state that
the immediate life-saving treatment for tension pneumothorax is needle decompression but there are case reports describing
patients with tension pneumothorax managed successfully by chest tube drainage,
without performing immediate needle decompression (10). Many experts would proceed directly to definitive treatment and bypass the step of needle decompression if the
capability to perform tube thoracostomy is
immediately available, and this is what we
opted for.
Classical signs of pneumothorax may be
masked during general anesthesia. In mechanically ventilated patients, the physician may suspect tension pneumothorax
when there is an increase in pleural pressures necessitating an increase in peak airway pressure in order to deliver the same
TV. Decreased expiratory volumes secondary to air leakage into the pleural space and
increased end-expiratory pressure, even after discontinuation of PEEP, are two other
Heart, Lung and Vessels. 2014, Vol. 6
Tension pneumothorax during cardiac surgery
signs of tension pneumothorax in these
patients. Increased PAP and decreased
CO or CI are other parameters suggestive
of tension pneumothorax (6-9). Hemodynamic instability, hypoxia and/or increased
oxygen requirements occur within minutes
during positive pressure ventilation in comparison to hours during spontaneous respiration (11). In our case there were many
signs indicating tension pneumothorax,
such as a decrease in expiratory TV followed by increase in PADP, decrease in CO
and CI leading to hemodynamic instability
and lastly subcutaneous emphysema. However, since most of the signs also indicate
hypovolaemia and contractile deficit that
may occur frequently during OPCAB, this
may lead to delay in diagnosis and treatment of the condition.
We hypothesize that at the time of the first
episode, start of a small pneumothorax
resulted in reduction in minute volume
without hemodynamic or airway pressure
changes.
The pneumothorax slowly progressed resulting in the second episode which was
associated with hemodynamic changes
but since the chest was still partially open
the hemodynamics could be stabilized by
fluid administration and inotropic support. However after chest closure the tension pneumothorax caused rapid, profound
hemodynamic changes in the now closed
chest cavity. We would like to highlight that
intraoperative tension pneumothorax may
definitely manifest after chest closure in
cardiac surgical procedures.
We conclude that the diagnosis of tension pneumothorax remains a challenge
in mechanically ventilated patients under
anesthesia. The presence of a cardiogenic
shock-like picture, poor response to inotropes, increased inspiratory airway pressure,
loss of tidal volume in a patient undergoing
cardiac surgery may also be due to a tension
pneumothorax.
REFERENCES
1. Rojas R, Wasserberger J, Balasubramaniam S. Unsuspected
tension pneumothorax as a hidden cause of unsuccessful
resuscitation. Ann Emerg Med 1983; 12: 411-2.
2. Watts BL, Howell MA. Tension pneumothorax: a difficult
diagnosis. Emerg Med J 2001; 18: 319-20.
3. Gold MI, Joseph SI. Bilateral tension pneumothorax following induction of anesthesia in two patients with chronic
obstructive airway disease. Anesthesiology 1973; 38: 93-6.
4. Smith CE, Otworth JR, Kaluszyk P. Bilateral tension pneumothorax due to a defective anesthesia breathing circuit
filter. J Clin Anesth 1991; 3: 229-34.
5. Ibrahim AE, Stanwood PL, Freund PR. Pneumothorax and
systemic air embolism during positive-pressure ventilation.
Anesthesiology 1999; 90: 1479-81.
6. Gustman P, Yerger L, Wanner A. Immediate cardiovascular
effects of tension pneumothorax. Am Rev Respir Dis 1983;
127: 171-4.
7. McLoud TC, Barash PG, Ravin CE, Mandel SD. Elevation
of pulmonary artery pressure as a sign of pulmonary barotrauma (Pneumothorax). Crit Care Med 1978; 6: 81-4.
8. Yu PYH, Lee LW. Pulmonary artery pressures with tension
pneumotorax. Can J Anaesth 1990; 37: 584-6.
9. Connolly JP. Hemodynamic measurements during a tensión pneumotorax. Crit Care Med 1993; 21: 294-6.
10. Boon D, Llewellyn T, Rushton P. A strange case of tension
pneumothorax. Emerg Med J 2002; 19: 470-471.
11. Derek J Roberts, Simon Leigh-Smith, Peter D Faris, Chad
G Ball, Helen Lee Robertson, Christopher Blackmore, et al.
Clinical manifestations of tension pneumothorax: protocol
for a systematic review and meta-analysis. Systematic Reviews 2014; 3: 3.
Cite this article as: Jain A, Arora D, Juneja R, Mehta Y, Trehan N. Life threatening tension pneumothorax during cardiac
surgery. A case report. Heart, Lung and Vessels. 2014; 6(3): 204-207.
Source of Support: Nil. Disclosures: None declared.
Heart, Lung and Vessels. 2014, Vol. 6
207
IMAGES IN MEDICINE
Heart, Lung and Vessels. 2014; 6(3): 208-209
208
Coronary to extra-cardiac anastomosis
A. Mohsen, J. Loughran, S. Ikram
Division of Cardiology, University of Louisville, KY, USA
Keywords: collaterals, coronary to extra-cardiac
anastomosis, coarctation of the aorta.
We are reporting a rare case of a patient
with the right coronary artery giving a large
collateral vessel to an intercostal artery in a
patient with repaired coarctation of aorta.
A 64 year-old man with coarctation of the
aorta, surgically repaired at 18 years of age,
presented with dyspnea. A trans-esophageal
echocardiogram revealed a severely stenotic
bicuspid aortic valve.
A
Corresponding author:
Sohail Ikram, M.D.
University of Louisville
Department of Cardiology
550 South Jackson Street
ACB, 3rd floor
Louisville, KY 40202
e-mail: [email protected]
A coronary angiogram was performed prior
to valve surgery. A left anterior oblique caudal cineangiographic view of the coronary
anatomy revealed a very long collateral vessel arising from the conus branch of the right
coronary artery that appeared to insert into
a hypertrophied blood vessel terminating
in the left thorax. The distal portion of this
vessel exhibited minimal motion with ventricular contraction, and appeared fixed to
the chest wall, suggesting this was a prominent intercostal artery (Figures 1 A, B).
B
Figures 1 A, B - Left anterior oblique caudal
cineangiographic view of the coronary anatomy
revealing a very long collateral vessel arising from
the conus branch of the right coronary artery that
appeared to insert into a hypertrophied blood vessel
terminating in the left thorax. The distal portion of
this vessel exhibited minimal motion with ventricular contraction, and appeared fixed to the chest wall
suggesting this was a prominent intercostal artery.
Heart, Lung and Vessels. 2014, Vol. 6
Coronary to extra-cardiac anastomosis
pensatory mechanism to bypass the stenosis in patients with aortic coarctation (1).
Collaterals from the thyrocervical trunk,
thoracic arteries arising from the axillary
artery and the internal mammary arteries
are most commonly observed (2).
Coronary collateral circulation within the
heart is a well-known phenomenon (3). Extracardiac-to-coronary anastomosis is gaining more attention (4).
The most common types of extracardiac-tocoronary anastomoses are from the internal
mammary artery and the bronchial arteries. Both typically occur in the presence of a
chronic occlusion of a coronary artery.
To our knowledge this is the first reporting
of coronary-to-extracardiac anastomoses.
Figure 2 - Left anterior oblique cranial view of
the aortic arch demonstrating dilated vessels arising from the arch proximal to the surgically corrected stenosis.
These findings are consistent with clinical history
of coarctation of aorta.
The left anterior oblique cranial view of
the aortic arch demonstrated dilated vessels
arising from the arch proximal to the surgically corrected stenosis (Figure 2).
This collateralization is an imperative com-
REFERENCES
1. Gross RE. Coarctation of the aorta. Circulation. 1953.
5:757-68.
2. Keane JF, Flyer DC. Coarctation of the aorta. In: Nadas’
Pediatric Cardiology, 2nd Ed., Keane JF, Lock JE, and Fyler
DC. (Eds), Saunders Elsevier, Philadelphia 2006; 627.
3. Traupe T, Gloekler S, de Marchi SF, Werner GS, Seiler C.
Assessment of the human coronary collateral circulation.
Circulation. 2010; 122: 1210-20.
4. Unger EF, Sheffield CD, Epstein SE. Creation of anastomoses between an extracardiac artery and the coronary circulation. Proof that myocardial angiogenesis occurs and can
provide nutritional blood flow to the myocardium. Circulation. 1990. 82: 1449-66.
Cite this article as: Mohsen A, Loughran J, Ikram S.Coronary to extra-cardiac anastomosis. Heart, Lung and Vessels. 2014;
6(3): 208-209.
Source of Support: Nil. Disclosures: None declared.
Heart, Lung and Vessels. 2014, Vol. 6
209
IMAGES IN MEDICINE
Heart, Lung and Vessels. 2014; 6(3): 210-212
210
Internal thoracic vein:
friend or foe?
A. Roubelakis, D. Karangelis, S.K. Ohri
Department of Cardiothoracic Surgery, Southampton University Hospitals NHS FoundationTrust, Southampton, UK
Keywords: graft elongation, coronary artery bypass,
revascularization.
The internal thoracic vein is a conduit that
has not been thoroughly investigated in literature as long term patency and outcomes
are unknown.
We present a case where the right internal
thoracic vein (RITV) was used to extend a
short right internal thoracic artery (RITA).
The elongated composite conduit was then
anastomosed to the right coronary artery
(RCA).
A 61-year-old male patient was referred
electively for a coronary artery bypass
grafting (CABG) operation.
The patient had undergone extensive
stenting to the left and right coronary artery systems. Unfortunately the stents to
the right coronary artery had restenosed
causing significant symptoms necessitating
revascularization (Figure 1).
From the conduit point of view, the patient had his long saphenous veins fully
stripped bilaterally. His radial arteries
were assessed with Allen’s test and use of
saturation monitor: following the occlusion of the radial the saturations failed to
rise, therefore they were deemed unusable.
RITA was therefore elected to be the conduit of choice.
Corresponding author:
Dimos Karangelis MD, PhD
Wessex Cardiac Centre
Southampton University Hospitals
FoundationT NHS Trust
Tremona Road, Hampshire, UK
e-mail: [email protected]
Figure 1 - Preoperative angiogram showing an instent occlusion of the mid-distal RCA.
RCA = right coronary artery.
The operation was performed in a standard
on-pump fashion. RITA was harvested initially as a pedicled graft.
The target vessel was measuring approximately 1.5 mm in diameter and was opened
distally due to the presence of the previous
stents and the anatomy of the lesions. Unfortunately RITA intima was found to be
of suboptimal quality and calibre distally
and had to be shortened.
This resulted in RITA length being insufficient to reach the target vessel, even with
skeletonisation. RITA was then extended
with a 2-3 cm segment of RITV which appeared to be of good quality and calibre.
The reversed RITV and RITA were anastomosed in an end-to-end fashion using
continuous 8-0 polypropylene suture (Figure 2).
The composite graft was then anastomosed
Heart, Lung and Vessels. 2014, Vol. 6
Internal thoracic vein: friend or foe?
211
Figure 2 - The end to end anastomosis (circled) between the RITA and RITV. There is no mismatch in
the calibre of the two vessels.
RITA=right internal thoracic artery; RITV = right
internal thoracic vein.
Figure 3 - The composite conduit as viewed from
the patient’s head after the completion of the distal
anastomosis.
distally to the RCA (Figure 3) and proximally to the ascending aorta. There was
excellent flow down this graft. The operation was completed uneventfully and the
patient was discharged home on the 5th
postoperative day. He remains symptomfree at a 6 month follow up.
The ITV conduit studies in literature are
very limited as they have not being used
routinely, therefore long term results are
unknown. The use of any other venous
conduit (like short saphenous or cephalic
veins) was not preferred due to patient’s
age and would also lead to significant size
mismatch between the RITA and the vein,
if used as extentions. Left internal thoracic
artery (LITA) needed to be preserved for
possible future revascularization on the
left coronary system. The use of gastroepiploic artery is not performed routinely in
our unit and therefore experience is very
limited.
There is only one study in literature where
ITVs were used as CABG grafts to the left
anterior descending artery in a minipig
model. The authors measured significant
intimal hyperplasia in these grafts after 4
weeks (1). Similar studies to humans however have not been performed.
A report from 1990 presented a 57 year old
Heart, Lung and Vessels. 2014, Vol. 6
A. Roubelakis, et al.
212
patient who underwent CABG operation
with the use of left and right ITAs and internal mammary vein (IMV). to an obtuse marginal. Angiography after 10 days revealed
excellent patency of the IMV graft (2).
It is difficult to justify the use of internal
thoracic veins as conduits for CABG, as in
most cases there is ample selection of other
well established conduits. The calibre of
these veins is similar to internal mammary
arteries (IMAs) and could potentially be
used as extensions. ITA elongation has
been described before with the utilization
of various grafts (3,4). To summarise, our
method could potentially be useful when
the internal mammary artery is not long
enough to reach the target vessel when no
other option is possible.
The major limitation of this report is that
a postoperative angiogram to assess the
patency of the graft could not be obtained.
There is no need of ethical committee approval for this case report. Written informed consent was obtained from the patient.
REFERENCES
1. Popov AF, Dorge H, Hinz J, Schmitto JD, Stojanovic T,
Seipelt R, et al. Accelerated intimal hyperplasia in aortocoronary internal mammary vein grafts in minipigs. J Cardiothorac Surg. 2008; 3: 20.
2. Stephan Y, Jebara VA, Fabiani JN, Carpentier A. The internal mammary vein: a new conduit for coronary artery
bypass. J. Thorac. Cardiovasc. Surg. 1990; 99: 178.
3. Calafiore AM, Teodori G, Di Giammarco G, Vitolla G,
Contini M, Maddestra N, et al. Left internal mammary
elongation with inferior epigastric artery in minimally invasive coronary surgery. Eur J Cardiothorac Surg. 1997;
12: 393-6; discussion 397-8.
4. Bernet FH, Hirschmann MT, Reineke D, Grapow
M, Zerkowski HR. Clinical outcome after composite grafting of calcified left anterior descending arteries. J Cardiovasc Surg (Torino) 2006; 47: 569-74.
Cite this article as: Roubelakis A, Karangelis D, Ohri SK. Internal thoracic vein: friend or foe? Heart, Lung and Vessels. 2014;
6(3): 210-212.
Source of Support: Nil. Disclosures: None declared.
Acknowledgment: We thank Anne Gale for editorial assistance.
Heart, Lung and Vessels. 2014, Vol. 6
FUTURE EVENTS
Calendar for future meetings
Intensive Care, Surgery and Cardiovascular Anesthesia
2014
October 4-7. Congress Australian Society of Anesthesiologists. Gold
Coast, Australia. Info: www.asa2014.com.au
October 11-15. 28th Annual Meeting European Association of Cardiothoraic Surgery. Milan, Italy. Info: www.eacts.org
October 12. Roland Hetzer International Cardiothoracic and Vascular
Surgery Society (RHICS) 8th Expert Forum during the 28th annual
EACTS Meeting, Milan Italy. Info: [email protected]
October 11-15. ASA Annual Meeting. New Orleans. LA
Info: www.asahq.org
October 26-30. American College of Surgeons Clinical Congress. San
Francisco, CA. Info: [email protected]
November 5-8. 61st Annual Meeting STSA. Tucson, AZ.
Info: [email protected]
November 6-8. 91st Annual Scientific Meeting of the Korean Society of
Anesthesiologists. Seoul, Korea. Info: www.ksa-conference.org
November 6-8. Annual Scientific Meeting Australian and New Zealand
College of Perfusionists. Auckland, New Zealand.
Info: [email protected]
November 14. ESA Focus Meeting on Peri-Operative Medicine: The pediatric patient. Athens, Greece. [email protected]
November 29. Roland Hetzer International Cardiothoracic and Vascular Surgery Society (RHICS) 9th Expert Forum. In cooperation with
the 9th Asian Cardiothoracic Surgery Specialty Update Course of
Chinese University of Hong Kong, Prince of Wales Hospital, Hong
Kong. Info: [email protected]
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December 12-16. Postgraduate Assembly, New York State Society of
Anesthesiologists. New York, NY. Info: www.nyssa-pga.org
2015
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Info: www.sccm.org
January 18-24. 33rd Annual Symposium: Clinical Update in Anesthesiology, Surgery and Perioperative Medicine. Four free workshops. St.
Kitts, West Indies. Info: [email protected]
February 11-15. 35th Annual Cardiothoracic Surgery Symposium CREF.
San Diego, CA. Info: www.crefmeeting.com
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Snowmass, CO. Info: [email protected]
March 17-20. 35th International Symposium on Intensive Care and
Emergency Medicine. Brussels, Belgium. Info: www.intensive.org
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Emergency Medicine. Brussels, Belgium. Info: www.intensive.org
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April 15-18. 8th International Symposium: Diabetes, Hypertension,
Metabolic Syndrome. Berlin, Germany.
Info: www.comtecmed.com/DIP
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Info: www.aats.org
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May 28-June 2. ESA Annual Meeting, Berlin, Germany.
Info: [email protected]
June 4-6.3rd International Symposium: Perioperative Care for Seniors.
Prague, Czech Republic. Info: www.anesthesiaforsenior2015.cz
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Info: [email protected]
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Medicine, Seoul, Korea. Info: www.wfsiccm2015.com
September 17-20. Canadian Association of Thoracic Surgeons. Montreal, Canada. Info: [email protected]
October 24-28. ASA Annual Meeting. San Diego, CA.
Info: www.asahq.org
November 9-10. Surgery of the Aorta. Bologna, Italy. Info: www.noemacongressi.it
December 11-15. Sixty-Ninth Postgraduate Assembly. New York Stat of
Anesthesiologists. New York, NY. Info: www.nyssa-pga.org
2016
January 16-23. 34th Annual Symposium: Clinical Update in Anesthesiology, Surgery and Perioperative Medicine. San Juan. Puerto Rico.
Info: [email protected]
March 22-25. 36th International Symposium on Intensive Care and
Emergency Medicine, Brussels, Belgium, Info: www.intensive.org
August 28-September 2. 16th World Congress of Anesthesiologists Hong
Kong. Info: www.WCA2016.com
2020
September. 17th World Congress of Anesthesiologists. Prague, Czech Republic. Info: www.csarim2020.cz
“Heart, Lung and Vessels” welcomes announcements of interest to physicians, researchers and others concerned with cardiothoracic and vascular surgery, 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
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all figures should be included in the file with the
text (on a new page after the reference list) and
should not appear on the figures themselves.
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.
Abbreviations. Except for units of measurement,
abbreviations are strongly discouraged. The first
time an abbreviation appears, it should be preceded by the words for which it stands (except for
units of measurement).
No abbreviations are allowed in the abstract.
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.
“Heart, Lung and Vessels” 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 will have
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”
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. “Heart, Lung and Vessels” is the
owner of all copyright to any published work.
“Heart, Lung and Vessels” and its licensees have
the right to use, reproduce, transmit, derive works
from, publish and distribute the contribution in
the “Heart, Lung and Vessels” or otherwise in any
form or medium. Authors may not use or authorize the use of the contribution without the written consent of “Heart, Lung and Vessels”.
EDITING SERVICES
“Heart, Lung and Vessels” offers high quality
editing service of English language revision and
statistical and methodological support, applying convenient low rates to authors who wish
to publish in peer-reviewed journals. While no
guarantee for article acceptance can be made,
improved English structure, appropriate scientific methodology and statistical revision can
greatly enhance the readability and message
of a paper, increasing its possibility to be published in major international peer reviewed
journals.
For information and tariffs please contact Lara
Sussani [email protected]
Please direct any questions to editorialoffice@
heartlungandvessels.org or visit http://www.heartlungandvessels.org/ “Heart, Lung and Vessels” editorial offices are located in the Department of Anesthesia and Intensive Care at 60 Via Olgettina, Milan, Italy 20132, tel. (+39) 02.26436158, fax (+39)
02.26436152, Lara Sussani email: editorialoffice@
heartlungandvessels.org
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