UNIVERSITATIS OULUENSIS MEDICA ACTA D D 1367 ACTA Antonino S. Rubino OULU 2016 D 1367 Antonino S. Rubino EFFICACY OF THE PERCEVAL SUTURELESS AORTIC VALVE BIOPROSTHESIS IN THE TREATMENT OF AORTIC VALVE STENOSIS UNIVERSITY OF OULU GRADUATE SCHOOL; UNIVERSITY OF OULU, FACULTY OF MEDICINE; MEDICAL RESEARCH CENTER OULU; OULU UNIVERSITY HOSPITAL
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UNIVERSITY OF OULU P .O. Box 8000 F I -90014 UNIVERSITY OF OULU FINLAND
A C T A U N I V E R S I T A T I S O U L U E N S I S
Professor Esa Hohtola
University Lecturer Santeri Palviainen
Postdoctoral research fellow Sanna Taskila
Professor Olli Vuolteenaho
University Lecturer Veli-Matti Ulvinen
Director Sinikka Eskelinen
Professor Jari Juga
University Lecturer Anu Soikkeli
Professor Olli Vuolteenaho
Publications Editor Kirsti Nurkkala
ISBN 978-952-62-1227-2 (Paperback)ISBN 978-952-62-1228-9 (PDF)ISSN 0355-3221 (Print)ISSN 1796-2234 (Online)
U N I V E R S I TAT I S O U L U E N S I S
MEDICA
ACTAD
D 1367
ACTA
Antonino S. R
ubino
OULU 2016
D 1367
Antonino S. Rubino
EFFICACY OF THE PERCEVAL SUTURELESS AORTIC VALVE BIOPROSTHESIS IN THE TREATMENT OF AORTIC VALVE STENOSIS
UNIVERSITY OF OULU GRADUATE SCHOOL;UNIVERSITY OF OULU,FACULTY OF MEDICINE;MEDICAL RESEARCH CENTER OULU;OULU UNIVERSITY HOSPITAL
A C T A U N I V E R S I T A T I S O U L U E N S I SD M e d i c a 1 3 6 7
ANTONINO S. RUBINO
EFFICACY OF THE PERCEVAL SUTURELESS AORTIC VALVE BIOPROSTHESIS IN THE TREATMENT OF AORTIC VALVE STENOSIS
Academic Dissertation to be presented with the assent ofthe Doctora l Train ing Committee of Health andBiosciences of the University of Oulu for public defence inAuditorium 1 of Oulu University Hospital, on 3 June2016, at 12 noon
Supervised byProfessor Fausto BiancariProfessor Tatu Juvonen
Reviewed byDocent Juha NissinenDocent Otso Järvinen
ISBN 978-952-62-1227-2 (Paperback)ISBN 978-952-62-1228-9 (PDF)
ISSN 0355-3221 (Printed)ISSN 1796-2234 (Online)
Cover DesignRaimo Ahonen
JUVENES PRINTTAMPERE 2016
OpponentDocent Peter Raivio
Rubino, Antonino S., Efficacy of the Perceval sutureless aortic valve bioprosthesisin the treatment of aortic valve stenosis. University of Oulu Graduate School; University of Oulu, Faculty of Medicine; MedicalResearch Center Oulu; Oulu University HospitalActa Univ. Oul. D 1367, 2016University of Oulu, P.O. Box 8000, FI-90014 University of Oulu, Finland
Abstract
Aortic valve stenosis (AS) is one of the most diffuse valvular diseases in developed countries. ASis a progressive disease, which usually results in serious life-threatening adverse events. Defininga treatment strategy for AS is a focus of cardiovascular research, although the topic is stillcontroversial because of its related clinical and economical implications.
Surgical aortic valve replacement (AVR),which is regarded as the gold standard for thetreatment of severe symptomatic AS, affords excellent results, particularly in asymptomaticpatients with good functional status. AVR requires the institution of cardiopulmonary bypass andaortic cross-clamping, and the duration of these procedures is directly associated with increasingmorbidity and mortality, especially in patients with preoperative comorbidities.
Accordingly, techniques aimed at decreasing the duration of cardiopulmonary bypass andaortic cross-clamping have the potential to improve postoperative outcomes of AVR.
In the present study, we demonstrated that the Perceval sutureless bioprosthesis couldsignificantly reduce the duration of the surgical procedure. This was associated with improvedimmediate postoperative outcomes and long-term freedom from adverse events.
The use of a Perceval sutureless bioprosthesis can facilitate AVR through minimally invasiveapproaches and is associated with fewer transfusions of packed red cells compared to fullsternotomy approaches, even with traditional stented bioprostheses. It could be expected thatpatients at intermediate-high risk would benefit more from the combination of a fast surgicalprocedure, performed with reduced surgical invasiveness.
When compared to transcatheter aortic valve implantation (TAVI), the Perceval suturelessbioprosthesis was associated with increased incidence of device success as well as lessparavalvular leak, with similar immediate and 1-year outcomes.
Finally, AVR with the Perceval sutureless bioprosthesis provided excellent hemodynamics atrest and under high workload. The significant increase of effective orifice area under stresssuggests that the Perceval sutureless bioprosthesis is the valve of choice for patients with smallaortic annuli or when prosthesis-patient mismatch is anticipated.
Keywords: aortic stenosis, aortic valve replacement, cross-clamping time, sutureless
Rubino, Antonino S., Ompeleettoman biologisen Perceval-aorttaläppäproteesintehokkuus aorttaläpän ahtauman hoidossa. Oulun yliopiston tutkijakoulu; Oulun yliopisto, Lääketieteellinen tiedekunta; Medical ResearchCenter Oulu; Oulun yliopistollinen sairaalaActa Univ. Oul. D 1367, 2016Oulun yliopisto, PL 8000, 90014 Oulun yliopisto
Tiivistelmä
Aorttaläpän ahtauma on yksi yleisimmistä läppävioista kehittyneissä maissa. Aorttaläpänahtauma on etenevä sairaus, joka yleensä johtaa vakaviin henkeä uhkaaviin haittatapahtumiin.Aorttaläpän ahtauman hoitotavasta keskustellaan kiivaasti sydän- ja verisuonitautien tutkimuk-sessa siihen liittyvien kliinisten ja taloudellisten vaikutusten vuoksi.
Aorttaläppäleikkausta, jossa aorttaläppä korvataan proteesilla, on aina pidetty vaikean oirei-sen aorttaläpän ahtauman hoidon kultaisena standardina, koska sen tulokset ovat erinomaisia,etenkin oireettomilla potilailla, joilla sydämen toiminta on hyvä. Leikkaus vaatii sydän-keuhko-koneen käyttöä ja aortan sulkemista, joiden kesto on suoraan yhteydessä kasvavaan sairastavuu-teen ja kuolleisuuteen erityisesti potilailla, joilla on muitakin sairauksia.
Niinpä tekniikat, jotka lyhentävät sydän-keuhkokoneen käyttöaikaa ja aortan sulkuaikaa, voi-vat mahdollisesti parantaa aorttaläppäleikkauksen tuloksia.
Tässä tutkimuksessa osoitettiin, että ompeleettoman biologisen Perceval-läppäproteesin käyt-tö vähensi merkittävästi leikkauksen kestoa. Tämä oli yhteydessä parantuneisiin lyhyen ja pit-kän aikavälin tuloksiin leikkauksen jälkeen.
Ompeleettoman biologisen Perceval-läppäproteesin käyttö voi helpottaa aorttaläppäleikkaus-ta, koska se voidaan asentaa vähemmän kajoavasta avauksesta, ja siihen liittyy vähemmän puna-solusiirtoja rintalastan kokoavaukseen verrattuna, myös silloin kun käytetään kokoavausta japerinteisiä stenttibioproteeseja. Voisi olla odotettavaa, että keskisuuren tai suuren riskin potilaathyötyisivät enemmän leikkauksesta, jossa yhdistyvät toimenpiteen nopeus ja vähäisempi kajoa-vuus.
Katetriteitse asennettuun biologiseen keinoläppään (TAVI) verrattuna ompeleeton biologinenPerceval-läppäproteesi oli yhteydessä parempaan laitteen toimimiseen ja pienempään paravalvu-laariseen vuotoon. Muut tulokset heti leikkauksen jälkeen ja yhden vuoden seurannassa olivatsamanlaisia.
Lopuksi voidaan todeta, että aorttaläppäleikkaukseen ompeleettomalla biologisella Perceval-läppäproteesilla liittyi erinomainen hemodynamiikka levossa ja korkean työkuorman aikana.Stressin aikaisen tehokkaan aorttaläpän aukon pinta-alan merkittävä kasvu osoittaa, että ompe-leeton biologinen Perceval-läppäproteesi on hyvä valinta potilaille, joilla on pieni aorttaläpänaukko tai kun on odotettavissa proteesin ja potilaan yhteensopimattomuutta.
The present study was conducted at the Cardiac Surgery Unit, Azienda
Ospedaliero-Universitaria “Policlinico-Vittorio Emanuele”, University of Catania,
Italy as well as Department of Cardiology and Cardiovascular Surgery, Centro
Clinico-Diagnostico “G.B. Morgagni” in Pedara (CT), Italy, during the years
2015-2016.
First of all, I had to express my full gratitude to my principal supervisor
Professor Fausto Biancari. Since we met for the first time during a congress in
Tampere, you recognized in me the attitude to research that you always have
prompted me to express at the best of my possibilities. You have supported me
during these last three years, helping me to achieve great goals, such as my first
AATS oral presentation. But, above all, I thank you for the opportunity to build a
strong friendship that lasts despite the great distances between Italy and Finland.
I want to thank my second supervisor Professor Tatu Juvonen for his
commitment in supervisoring me during my Doctoral program.
I sincerely thank my pre-examiners Docent Juha Nissinen and Docent Otso
Järvinen for academic revision of the manuscript of the thesis. The comments you
have expressed on my as thesis have helped me in impriving the quality of the
dissertation markedly. I also want to thank Ph.D. Deborah Kaska for careful
revision of the language and Eeva-Maja Kinnunen, MD PhD for revision of the
Finnish abstract.
I wish to thank the members of my follow-up group, Professor Pekka Rainio,
Professor Jouni Heikkinen and Professor Jarmo Lahtinen for your valuable and
encouraging feedback regarding the original articles as well as the progress of the
entire project.
I want to thank particularly Doctor Carmelo Mignosa, my Chief, mentor and
friend. You support me during my surgical training and always give me the
opportunity to have a particular exposure at several international meetings.
My special thanks go also to all the co-authors of the original articles for
collaboration. I believe that this experience have helped all of us to establish an
extensive cooperation between all our Institutions.
I am particularly grateful to Wanda Deste, Gianni Millan and the residents of
the School of Cardiology of the University of Catania for their support during all
the echocardiographic studies performed. A particular thank to Vincenzo Lavanco
and Vincenzo Caruso for their deep involvement in the project.
10
My deepest gratitude and love goes to my parents, Angela e Guido. You have
always loved and encouraged me during all my life, at first as a child,
subsequently as a student and now as a father and husband. You are the examples
I want to give to my children.
Finally, my deepest and absolute love goes to my wife Lucia. I try with all
my efforts to give you a lovely life, but I cannot match what you have given me:
our children.
Catania, April 2016 Antonino S. Rubino
11
Abbreviations
Ao aorta
AS aortic stenosis
AVA(i) aortic valve area (index)
AVR aortic valve replacement
CABG coronary artery bypass graft
CSA cross sectional area
DSE dobutamine stress echocardiography
DVI dimensionless velocity index
EOA(i) effective orifice area (index)
HR hazard ratio
LVEF left ventricular ejection fraction
LVOT left ventricular outflow tract
PPM prosthesis-patient mismatch
SV stroke volume
TAVI transcatheter aortic valve implantation
VTI velocity-time integral
12
13
Original publications
This thesis is based on the following publications, which are referred throughout
the text by their Roman numerals:
I Rubino AS, Santarpino G, De Praetere H, Kasama K, Dalén M, Sartipy U, Lahtinen J, Heikkinen J, Deste W, Pollari F, Svenarud P, Meuris B, Fischlein T, Mignosa C & Biancari F (2014) Early and intermediate outcome after aortic valve replacement with a sutureless bioprosthesis: Results of a multicenter study. J Thorac Cardiovasc Surg 148:865–871.
II Dalén M, Biancari F, Rubino AS, Santarpino G, De Praetere H, Kasama K, Juvonen T, Deste W, Pollari F, Meuris B, Fischlein T, Mignosa C, Gatti G, Pappalardo A, Sartipy U & Svenarud P (2015) Mini-sternotomy versus full sternotomy aortic valve replacement with a sutureless bioprosthesis: a multicenter study. Ann Thorac Surg 99: 524–530.
III Dalén M, Biancari F, Rubino AS, Santarpino G, Glaser N, De Praetere H, Kasama K, Juvonen T, Deste W, Pollari F, Meuris B, Fischlein T, Mignosa C, Gatti G, Pappalardo A, Svenarud P &Sartipy U. (2016) Aortic valve replacement through full sternotomy with a stented bioprosthesis versus minimally invasive sternotomy with a sutureless bioprosthesis. Eur J Cardiothorac Surg 49: 220–227
IV D'Onofrio A, Salizzoni S, Rubino AS, Besola L, Filippini C, Alfieri O, Colombo A, Agrifoglio M, Fischlein T, Rapetto F, Tarantini G, Dalèn M, Gabbieri D, Meuris B, Savini C, Gatti G, Aiello ML, Biancari F, Livi U, Stefàno PL, Cassese M, Borrello B, Rinaldi M, Mignosa C & Gerosa G; Italian Transcatheter Balloon-Expandable Registry and the Sutureless Aortic Valve Implantation Research Groups. (In press) The rise of new technologies for aortic valve stenosis: A comparison of sutureless and transcatheter aortic valve implantation. J Thorac Cardiovasc Surg
V Biancari F, Barbanti M, Santarpino G, Deste W, Tamburino C, Gulino S, Immè S, Di Simone E, Todaro D, Pollari F, Fischlein T, Kasama K, Meuris B, Dalén M, Sartipy U, Svenarud P, Lahtinen J, Heikkinen J, Juvonen T, Gatti G, Pappalardo A, Mignosa C & Rubino AS (2015) Immediate outcome after sutureless versus transcatheter aortic valve replacement. Heart Vessels 31: 427–433.
VI Rubino AS, Biancari F, Caruso V, Lavanco V, Privitera F, Rinaldi I Sanfilippo M, Millan G, D’Urso LV, Castorina S & Mignosa C (2016) Hemodynamic assessment of the Perceval sutureless valve by dobutamine stress echocardiography. (Manuscript)
Contributions of the author of the thesis:
I Conception and design of the study, acquisition of data, drafting the article,
revising it critically for important intellectual content, final approval of the
final version of the manuscript to be submitted.
14
II Conception and design of the study, acquisition of data, revising the article
critically for important intellectual content, final approval of the final version
of the manuscript to be submitted.
III Conception and design of the study, acquisition of data, revising the article
critically for important intellectual content, final approval of the final version
of the manuscript to be submitted.
IV Conception and design of the study, acquisition of data, drafting the article,
revising it critically for important intellectual content, final approval of the
final version of the manuscript to be submitted.
V Conception and design of the study, acquisition of data, drafting the article,
revising it critically for important intellectual content, final approval of the
final version of the manuscript to be submitted.
VI Conception and design of the study, acquisition of data, drafting the article,
revising it critically for important intellectual content, final approval of the
final version of the manuscript to be submitted.
15
Contents
Abstract
Tiivistelmä
Acknowledgements 9 Abbreviations 11 Original publications 13 Contents 15 1 Introduction 19 2 Review of the literature 21
2.1 Epidemiology of aortic valve stenosis .................................................... 21 2.2 Etiopathogenesis and pathology of aortic valve stenosis ........................ 21 2.3 Diagnosis of aortic valve stenosis ........................................................... 22 2.4 Natural history of aortic valve stenosis ................................................... 26 2.5 Indications for treatment of aortic valve stenosis .................................... 26 2.6 Risk factors for associated morbidity and mortality after surgical
2.7 The impact of minimally invasive approaches on outcomes after
AVR ......................................................................................................... 45 3 Aim of the research 47 4 Materials and methods 49
4.1 Study design and patient populations ...................................................... 49 4.2 Data collection and risk stratification ...................................................... 51
16
4.3 Operative technique ................................................................................ 51 4.4 Endpoints of the study ............................................................................. 52 4.5 Statistical analysis ................................................................................... 53
5 Results 55 5.1 In-hospital and mid-term outcomes after AVR with Perceval
bioprosthesis (I) ....................................................................................... 55 5.1.1 Octogenarians ............................................................................... 59 5.1.2 Operative outcomes after full sternotomy vs minimally
invasive approach ......................................................................... 60 5.2 Stratification of in-hospital mortality according to quartiles of
EuroSCORE II (I) ................................................................................... 60 5.3 Implantation of Perceval bioprosthesis with minimally invasive
approaches (II) ........................................................................................ 61 5.4 Comparison of minimally invasive Perceval implantation to the
traditional approach with full sternotomy and stented valves (III) ......... 68 5.5 In-hospital outcomes and 1-year survival after AVR with the
Perceval sutureless bioprosthesis vs TAVI (IV) ...................................... 76 5.5.1 Perceval sutureless bioprosthesis vs all TAVI ............................... 78 5.5.2 Perceval sutureless bioprosthesis vs transapical TAVI ................. 78 5.5.3 Perceval sutureless bioprosthesis vs trans-femoral TAVI ............. 79
5.6 Immediate outcomes after AVR with the Perceval sutureless
bioprosthesisvs TAVI (V) ........................................................................ 80 5.7 Hemodynamic assessment of the Perceval sutureless
bioprosthesis with dobutamine stress echocardiography (VI) ................. 86 5.7.1 Variation of EOA in patients with baseline prosthesis-
patient mismatch ........................................................................... 88 5.7.2 Variation of EOA according to valve size ..................................... 88
6 Discussion 91 6.1 Impact of AVR with the Perceval sutureless bioprosthesis on in-
hospital and mid-term outcomes (I) ........................................................ 91 6.2 Usefulness of the Perceval sutureless bioprosthesis in minimally
invasive AVR (II) .................................................................................... 92 6.3 Advantages of minimally invasive AVR with the Perceval
sutureless bioprosthesis compared to traditional surgery (III) ................ 93 6.4 Different outcomes for different techniques (IV) .................................... 94
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6.5 Spreading light on the “gray-zone” between traditional AVR and
TAVI (V) ................................................................................................. 96 6.6 A stentless valve with a sutureless technology (VI) ................................ 97
7 Conclusions 99 8 Future perspectives 101 List of references 103 Original publications 117
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1 Introduction
The treatment strategy for aortic valve stenosis (AS) is a controversial topic in
cardiovascular research, because of the related clinical and economic implications.
It has been estimated that AS is one of the most common valvular diseases in
developed countries, second only to mitral valve disease, with an incidence that is
expected to double in the next 50 years [1].
AS stenosis is a progressive disease, which usually results in serious life-
threatening adverse events [2]. The chronic increased impedance to forward flow
is compensated initially by an increase of left ventricular wall thickness, but
invariably leads to various degrees of ventricular failure if the valve pathology is
misdiagnosed or left untreated.
Surgical aortic valve replacement (AVR) has always been regarded as the
gold standard treatment for severe symptomatic aortic stenosis, with excellent
results, especially in asymptomatic patients with good functional status [3,4].
However, the incidence of postoperative complications parallels the number of
other comorbidities that range from age to diabetes, from organ failure to
associated cardiac and non-cardiac pathologies, and include patient frailty.
AVR requires inevitably the institution of cardiopulmonary bypass and aortic
cross-clamping, the duration of which is directly associated with increasing
morbidity and mortality [5,6], especially in high risk patients.Therefore, new
technologies designed to reduce the adverse events associated with this procedure
have recently been developed.
The Perceval sutureless valve (Sorin Group, Saluggia, Italy) (Figure 1) is a
novel aortic valve bioprosthesis with a unique design that facilitates its surgical
implantation with reduced duration of the surgical procedure. There is increasing
evidence that AVR with a sutureless bioprostheses is associated with favorable
outcomes in intermediate risk patients [7,8]. Its use is particularly attractive in
minimally invasive surgery [9–11].
20
Fig. 1. Perceval sutureless bioprosthesis is made of bovine pericardium, folded over a
nitinol stent.
Transcatheter aortic valve implantation (TAVI) provides excellent results in
patients at high or prohibitive surgical risk, and recently became a recommended
procedure for patients with absolute contraindications to surgery [12,13].
However, operative and follow-up results of TAVI in intermediate risk patients
are questionable, particularly because of the increased risk of incidence of
paravalvular leakage, which is a risk factor for adverse events.
This dissertation aims to clarify the effect of sutureless AVR on the
immediate operative morbidity and mortality, and to evaluate the durability of the
results at mid-term follow-up. In particular, the feasibility of a minimally invasive
implant will be investigated, also in comparison with traditional surgery
performed through full sternotomy and with the use of stented bioprostheses.
The potential benefits of sutureless AVR will be assessed in comparison to
TAVI, to ascertain which technique is preferred in intermediate risk patients with
severe AS.
Finally, the hemodynamic features of this valve will be examined under high
workload to ascertain if the indication to sutureless AVR could be extended also
to younger and physically active patients.
21
2 Review of the literature
2.1 Epidemiology of aortic valve stenosis
AS is one of the most prevalent valvular disease in the developed countries
[15,16].
A recent systematic review showed that the pooled prevalence in the general
European population aged 55–74 years and >75 years is 2.9% (1.5–4.3%) and
13.6% 8.3–18.9%), respectively [15]. In particular, 21.6% (19.1–24.2%) of these
patients have severe AS and 71.1% (62.7–79.4%)are symptomatic. According to
these figures, it has been estimated that almost 9.2 million Europeans aged ≥55
years have AS, almost 2 million have severe AS, 1.2 million are eligible for
surgical aortic valve replacement (AVR) and 230.000 for transcatheter aortic
valve implantation (TAVI)being considered at high risk for surgery [15].
Osnabrugge et al.[16]reporteda pooled prevalence of AS of 12.4% (6.6–
18.2%) among elderly patients aged ≥75 years. Of them, 3.4% (1.1–5.7%) have
severe AS, with 75.6% being symptomatic. These data account for almost 1
million people in Europe and 540 000 in North America that suffer from severe
symptomatic AS.
With the ageing of the population, the prevalence of AS is expected to
increase. Iung & Vahanian recently reported that in France, the number of patients
aged ≥75 years with at least moderate AS is expected to double over the next 50
years [1].
Accordingly AS has a significant impact on public health management as it
requires an increasing burden of health care resources utilization.
2.2 Etiopathogenesis and pathology of aortic valve stenosis
Aortic valve degeneration is a progressive disease that begins with leaflet
thickening thateventually leadsto severe calcifications within the aortic cusps.
This process has been frequently considered a natural evolution of the valve
opening and closing cycles and often addressed as a senile degeneration of valve
tissues [16].
However, recent studieshave demonstrated that the degenerative processes
leading to severe aortic stenosis encompass biological pathways similar to
atherogenesis and osteogenesis [16–18].
22
To better understand the etiopathogenesis of aortic valve degeneration, a
concise overview of the normal histology of the aortic valve is provided. The
aortic cusps are attached to the aortic wall in a semilunar fashion between the
three commissures. Vascular endothelial cells cover the valve on both the
ventricular and aortic sides. In between, there is a core of three layers of
interstitial cells in continuity with the supporting structures of the other valves,
but with differing extracellular matrix composition: the ventricularis (rich in
elastin), the spongiosa (rich in glycosaminoglycans) and the fibrosa (rich in
collagen).
The extracellular matrix is not directly involved in the degeneration process
of the aortic valve, as the role of the glycosaminoglycan layer is to facilitate the
rearrangements of the other two layers during the opening and closing cycles. On
the other hand, in vitro and in vivo studies have demonstrated that the interstitial
cells have the potential to promote osteogenesis and angiogenesis in response to
several stimuli, such as hypertension, elevated LDL concentrations, mechanical
stretch and stress on the leaflets or various inflammatory states associated with an
abnormal secretion of pro-inflammatory cytokines and growth factors. [16,17].
The remodeling process that eventually ends up in aortic stenosis can be
divided into two phases: an initiation phase with pathways similar to
atherogenesis (lipid deposition and inflammatory cascade activation), followed by
a propagation phase during which osteogenesis becomes prominent [18].
Briefly, endothelial injury is initiated by several stimuli (e.g. mechanical
stress, infections, systemic inflammation) with consequential lipid deposition and
oxidization in the interstitial layers. This promotes apoptosis with deposition of
microcalcifications. Endothelial injuries as well as increased mechanical stress in
the stiffer cusps initiate a pro-inflammatory cascade that is maintained in a self-
propagating loop. Accordingly, the interstitial cells initially produce a collagen
matrix (aortic sclerosis) and subsequently differentiate into osteoblast-like cells,
which are ultimately responsible for extensive calcium deposition over the
collagen scaffold. [17,18]
2.3 Diagnosis of aortic valve stenosis
Patients with suspected AS usually present with a heart murmur or abnormalities
in non-invasive tests. Regardless of the presentation, accurate history
investigation and physical examination should be performed in all patients with
23
suspect or already diagnosed AS. In fact, patients often report an absence of
symptoms because they have progressively limited their daily activities, and this
should also be considered as a symptom.
A physical examination is important to assess the general condition as well as
to reveal other comorbidities.
Electrocardiography and chest X-ray are useful to investigate heart rhythm
and to give an estimate of pulmonary functional capacity. Accordingly,
electrocardiography may unveil underlying atrial fibrillation, as well as different
degrees of bundle branch block. X-ray can illuminate pulmonary congestion as
well as an enlarged cardiac silhouette.
However, transthoracic echocardiography represents the gold standard to
confirm clinical suspects and to assess the severity of the lesion [19].
Criteria and methods for the management of valvular pathology have been
defined in the most recent 2009 guidelines of the American Society of
Echocardiography/ European Association of Echocardiography [20].
Peak aortic velocity
Peak aortic velocity is the most reliable predictor of poor outcome in patients with
AS [21]. It is measured with continuous wave Doppler from the best window
available (apical, suprasternal, right parasternal). The severity of AS is defined as
mild if the peak velocity is <2.9 m/sec, moderate if 3-3.9 m/sec and severe if >4.0
m/sec [13,20].
Transvalvular gradients
Peak and mean transvalvular gradients are measured with continuous wave
Doppler from the same windows and are a direct function of velocity. Peak
gradient is calculated as 4V2max according to the Bernoulli equation. Mean
gradients are calculated as the integral of the velocity trace during one systole. AS
is defined as mild if the mean gradient is <25 mmHg, moderate if 25-40 mmHg
and severe if >40 mmHg [13,20].
However, gradients are also linearly dependent on cardiac output (e.g. AS is
underestimated in case of hypovolemia, low output state, low ejection fraction)
and coexistent valvular diseases (increased gradients with associated aortic
regurgitation or decreased in case of associated mitral regurgitation).
24
Aortic valve area
Aortic valve area is calculated according to the continuity equation
(SVLVOT=SVAo). Stroke volume can be expressed as the product of the cross-
sectional area and velocity-time integral (SV=CSAxVTI). Therefore, aortic valve
area (AVA) can be calculated as CSALVOT x VTILVOT / VTIAo [13,20].
LVOT diameter is measured in meso-systole from a long-axis view. VTILVOT
is measured with pulsed wave Doppler from a 5- or 3-chambers view, VTIAo is
measured with pulsed wave Doppler from the best view. This calculation is
dimension-dependent as also minimal variations of the LVOT diameter are
squared.
AS is considered mild if AVA is 1.5-2 cm2, moderate if 1.0-1.5 cm2 and
severe if <1.0 cm2. AVA calculation can be indexed to body surface area (AVA
index). In this case, the thresholds for AS classification are as follows: mild >0.85
cm2/m2, moderate 0.85-0.6 cm2/m2, severe <0.6 cm2/m2 [13,20].
Similarly, the functional area of an aortic valve prosthesis (effective orifice
area – EOA) can be calculated with the continuity equation as well. The EOA
indexed to the body surface area is of particular clinical relevance, as an EOAi
<0.85 cm2/m2 is diagnostic for prosthesis-patient mismatch (PPM), with EOAi
<0.65 cm2/m2 considered to be a severe PPM [22].
Velocity ratio or dimensionless velocity index (DVI)
Starting from the assumption that a normal aortic valve area is equal to that of the
corresponding LVOT in each individual, the ratio between the peak velocities (or
VTI) in LVOT to that across the aortic valve represents a simple method to assess
the severity of valve stenosis.
Therefore, AS is considered mild if DVI is 0.5-1, moderate if 0.25-0.5 and
severe if <0.25. Since DVI incorporates the effect of flow on velocity through the
valve and is much less dependent on valve size, this method can be particularly
useful for screening for valve dysfunction [13,20].
Left ventricular geometry
The increased transaortic impedance to blood flow is compensated by a reactive
concentric hypertrophy of the left ventricle. Interventricular septum, left
ventricular diameters and posterior wall thickness are usually recorded during
25
transthoracic echocardiography and give an estimate of the left ventricular mass.
Relative wall thickness is a derived parameter that is helpful to discern between
concentric remodeling, concentric hypertrophy and eccentric hypertrophy [23,24]
(Figure 2).
Fig. 2. Definition of different degrees of ventricular remodeling according to left
ventricular mass index, relative wall thickness and gender [modified from MDMath,
Canadian Society of Echocardiography - http://csecho.ca/mdmath/?tag=lvmlvmi]
Left ventricular function
Left ventricular systolic and diastolic function is a mandatory evaluation in the
echocardiographic work-up for AS.
In fact, all the estimates of aortic valve stenosis or prosthesis dysfunction are
directly correlated to the flow generated across the valve. Accordingly, the
severity of stenosis or prosthesis dysfunction can be underestimated in case of
reduced ejection fraction. This is the case of the so called low-flow low-gradient
AS. Typically, this is observed in the case of AVA<1 cm2, peak velocity <4 m/sec
or mean gradient <40 mmHg and a LVEF ≤50% [25].
Dobutamine stress echocardiography (DSE) is therefore recommended to
discriminate between a fixed aortic stenosis (significant increase in gradients and
velocities without increasing valve area under DSE) and a moderate stenosis
(slight increase in gradients and velocities with a significant increase of valve
area under DSE). DSE is an interesting investigational tool to assess prosthetic
valve function as an alternative to exercise echocardiography [26].
26
2.4 Natural history of aortic valve stenosis
AS is a progressive disease and requires prompt treatment once diagnosed.
Generally, only 10-15% of patients with aortic sclerosis develop a stenosis over a
period of 2 to 5 years. However, when even mild stenosis is diagnosed, the
progression to severe obstruction is unavoidable, with an expected increase of
transvalvular velocity from 0.1 to 0.3 m/sec/year and an increase of mean
gradient from 3 to 10 mmHg/year as well as a reduction rate of valve area by 0.1
cm2/year. [27]
Patients with severe stenosis, left on medical therapy alone, experience a poor
outcome, with worsening of symptoms and an expected survival of 50% at 2
years and 20% at 5 years [28]. The approximate time interval after the onset of
symptoms to death is 2 years for heart failure, 3 years for syncope and 5 years for
angina [2].
Therefore, prompt treatment is required at the time of diagnosis, especially
after symptom onset. In particular, symptomatic patients undergoing AVR
experience similar long-term outcomes compared to asymptomatic operated
patients. Conversely, the outcome at follow-up is poorer if asymptomatic patients
are left untreated, and even worse if symptomatic patients are left to the natural
history of their aortic valve pathology [3,4,21].
2.5 Indications for treatment of aortic valve stenosis
The goals of intervention in AS are to relieve symptoms, enhance exercise
capacity and quality of life, and prolong life expectancy. The desired effects of
relieving the barrage to the left ventricle are improvements in left ventricular
function and a regression of hypertrophy.
The Joint Task Force on the Management of Valvular Heart Disease of the
European Society of Cardiology (ESC) and the European Association for Cardio-
Thoracic Surgery (EACTS) published in 2012 the Guidelines on the management
of valvular heart disease [29].
The American College of Cardiology/American Heart Association Task Force
on Practice Guidelines has renewed in 2014 the indications for the management
of patients with valvular heart disease [13].
As far as the treatment of aortic valve stenosis is considered, both guidelines
are overlapping either in terms of diagnosis or indications. Accordingly, in the
present dissertation the more recent ACC/AHA guidelines will be discussed.
27
In this last edition of the guidelines, patients with AS have been divided into
four stages according to symptoms:
– Stage A – at risk: asymptomatic patients with known risk factors;
– Stage B – progressive: asymptomatic patients with mild-to-moderate severity
of disease with a progressive worsening of valve dysfunction;
– Stage C – asymptomatic severe: asymptomatic patients with diagnosis of
severe valve disease with normal ventricular function (C1) or ventricular
dysfunction (C2);
– Stage D – symptomatic severe: patients who developed symptoms directly
correlated to the valve disease: high-gradient AS (D1); low-flow low-gradient
AS (D2); low-gradient AS with normal EF or paradoxical low-flow AS (D3).
Patients in Stage A do not need follow-up evaluations unless new onset of
symptoms occurs. Conversely, patients in Stage D have a clear indication for the
treatment of AS. In between, patients in Stage B and C need routine follow-up
evaluations to assess the progression of the disease. In particular, patients in Stage
B should be scheduled every 3-5 years in case of mild disease or with a 1-2 year
interval in case of moderate stenosis; on the other hand, patients in Stage C need a
close follow-up of 6-12 months [13].
Irrespective of the stage, all other pre-existing risk factors should be
addressed with optimal medical therapy, particularly systemic hypertension [30].
Moderate physical exercise should be encouraged in any case, when feasible.
The decision to intervene should be weighted against the inherent risk of the
procedure (either surgical or transcatheter) and the natural history of the disease.
Several scoring systems (e.g. STS and EuroSCORE II) are able to predict
immediate mortality after surgery and therefore should be taken into account in
any counseling for surgical risk stratification [13]. However, the comprehensive
clinical and instrumental assessment of the patient’s clinical conditions is
mandatory to unveil underlying pathologies that would impair the immediate
result of the procedure (e.g. pulmonary or liver dysfunction, neurological
disorders, frailty). Moreover, surgery should be planned correctly during
preoperative work-up, to exclude any technical impediment, such as porcelain
aorta in case of AVR (Table 1).
28
Ta
ble
1. R
isk
as
se
ssm
en
t co
mb
inin
g S
TS
PR
OM
, F
rail
ty,
Ma
jor
org
an
co
mo
rbid
itie
s a
nd
pro
ced
ure
-sp
ec
ific
im
pe
dim
en
t (a
dap
ted
fro
m N
ish
imu
ra e
t al 2
01
4 [
13])
.
Para
mete
r to
be c
onsi
dere
d
Low
Ris
k
(Mu
st m
ee
t A
LL
crite
ria
)
Inte
rmedia
te R
isk
(An
y 1
crite
rio
n)
Hig
h R
isk
(An
y 1
crite
rio
n)
Pro
hib
itive
Ris
k
(An
y 1
crite
rio
n)
ST
S P
RO
M
<4
%
4%
-8%
>
8%
P
red
icte
d r
isk
of
de
ath
or
ma
jor
org
an
com
orb
iditi
es
>50
% a
t 1
yea
r
Fra
ilty1
N
one
1 in
dex
≥2 in
dic
es
Ma
jor
pre
op
era
tive
org
an
co
mp
rom
ise n
ot
to
be im
pro
ved p
ost
opera
tively
None
1 o
rgan s
yste
m
No m
ore
than 2
org
an
syst
em
s
≥3 o
rgan s
yste
ms
Pro
cedure
-speci
fic im
pedim
ent2
N
one
P
oss
ible
P
oss
ible
S
eve
re
1 F
railt
y ca
n b
e a
ssess
ed b
y K
atz
Act
iviti
es
of
Daily
Liv
ing a
nd in
dep
ende
nce
in a
mbu
latio
n,
as
well
as
oth
er
scoring s
yste
ms
2 F
or
exa
mple
tra
cheost
om
y pre
sent,
heavi
ly c
alc
ified a
scendin
g a
ort
a, ch
est
malfo
rmatio
n,
art
erial c
oro
nary
gra
ft a
dhere
nt to
po
sterior
chest
wall,
or
radia
tion
dam
age
29
Accordingly, a multidisciplinary Heart Valve Team should evaluate the
patient preoperatively when treatment is considered [13].
In accordance with all the criteria already discussed, AVR is recommended in
the case of severe AS in symptomatic patients with preserved LVEF or in the case
of asymptomatic patients with LVEF≤50%. When another kind of cardiac surgery
is performed, the threshold for surgical procedure is also reducedforasymptomatic
patients with severe AS. Complete guidelines on indications for AVR are shown
in Table 2.
30
Ta
ble
2. T
imin
g t
o i
nte
rve
nti
on
(a
dap
ted
fro
m N
ish
imu
ra e
t al 2
01
4 [
13
]).
Reco
mm
end
atio
ns
Cla
ss o
f R
eco
mm
endatio
n
Leve
l of E
vide
nce
AV
R is
reco
mm
en
ded f
or
sym
pto
matic
patie
nts
with
se
vere
hig
h-g
radie
nt
AS
who h
ave
sym
pto
ms
I B
by
his
tory
or
on e
xerc
ise test
ing (
sta
ge D
1)
AV
R is
re
com
me
nd
ed
fo
r a
sym
pto
ma
tic p
atie
nts
with
seve
re A
S (
sta
ge
C2)
an
d L
VE
F <
50
%
I B
AV
R is
indic
ate
d f
or
patie
nts
with
se
vere
AS
(st
age C
or
D)
when u
nd
erg
oin
g o
ther
card
iac
surg
ery
I
B
AV
R is
reaso
nable
for
asy
mpto
matic
patie
nts
with
very
seve
re A
S (
stage C
1, aort
ic v
elo
city
≥5
.0
IIa
B
m/s
and lo
w s
urg
ical r
isk)
AV
R is
reaso
nable
in a
sym
pto
matic
patie
nts
(st
age C
1)
with
seve
re A
S a
nd d
ecr
ease
d e
xerc
ise
IIa
B
tole
rance
or
an e
xerc
ise fall
in b
lood p
ress
ure
AV
R is
reaso
nable
in s
ympto
matic
pa
tients
with
low
-flo
w/lo
w-g
radie
nt
seve
re A
S w
ith r
educe
d
IIa
B
LV
EF
(st
age D
2)
with
a lo
w-d
ose
do
buta
min
e s
tress
stu
dy
that sh
ow
s an a
ort
ic v
elo
city
≥4.0
m/s
(o
r m
ea
n p
ress
ure
gra
die
nt ≥4
0 m
m H
g)
with
a v
alv
e a
rea ≤
1.0
cm
2 a
t any
dobuta
min
e d
ose
AV
R is
reaso
nable
in s
ympto
matic
pa
tients
who h
ave
low
-flo
w/lo
w-g
radie
nt se
vere
AS
(st
age D
3)
IIa
C
wh
o a
re n
orm
ote
nsi
ve a
nd
ha
ve a
n L
VE
F ≥
50%
if c
linic
al,
hem
odyn
am
ic,
and a
nato
mic
data
support
valv
e o
bst
ruct
ion a
s th
e m
ost
like
ly c
ause
of
sym
pto
ms
AV
R is
re
aso
na
ble
fo
r p
atie
nts
with
mo
de
rate
AS
(st
ag
e B
) (a
ort
ic v
elo
city
3.0
–3
.9 m
/s)
wh
o a
re
IIa
C
underg
oin
g o
ther
card
iac
surg
ery
AV
R m
ay
be c
onsi
dere
d for
asy
mpto
matic
patie
nts
with
seve
re A
S (
stage C
1)
and r
apid
dis
ease
IIb
C
pro
gre
ssio
n a
nd lo
w s
urg
ica
l ris
k
AV
R =
aort
ic v
alv
e r
epla
cem
ent, A
S =
aort
ic s
tenosi
s, L
VE
F =
left v
entr
icula
r eje
ctio
n fra
ctio
n
31
As far as the choice of the procedure is concerned, surgery is the gold
standard for patients at low or intermediate surgical risk. However, the guidelines
support and encourage the role of the Heart Team in decision-making about
patients with high or prohibitive surgical risk, as TAVI is now becoming a
standard practice in many centers. Finally, whatever the kind of procedure to be
performed, there is no indication for patients at prohibitive surgical risk when life
expectancy is lower than 12 months (Table 3).
32
Ta
ble
3. C
ho
ice
of
su
rgic
al
ao
rtic
va
lve r
ep
lac
em
en
t o
r TA
VI
(ad
ap
ted
fro
m N
ish
imu
ra e
t al 2
01
4 [
13])
.
Reco
mm
end
atio
ns
C
lass
of
Reco
mm
endatio
n
Leve
l of E
vide
nce
Surg
ical A
VR
is r
eco
mm
ended in
patie
nts
who m
eet an
indic
atio
n f
or
AV
R w
ith lo
w o
r in
term
edia
te
I A
surg
ica
l ris
k
For
patie
nts
in w
hom
TA
VI
or
hig
h-r
isk
surg
ica
l AV
R is
bein
g c
onsi
dere
d,
mem
bers
of
a H
ea
rt T
eam
I
C
should
co
llabora
te to p
rovi
de o
ptim
al p
atie
nt ca
re
TA
VI
is r
eco
mm
en
de
d in
pa
tien
ts w
ho
me
et
an
ind
ica
tion
fo
r A
VR
fo
r A
S w
ho
ha
ve a
pro
hib
itive
I
B
surg
ica
l ris
k a
nd
a p
red
icte
d p
ost
-TA
VI
surv
iva
l >1
2 m
on
ths
TA
VI
is a
re
aso
na
ble
alte
rna
tive
to
surg
ica
l AV
R in
patie
nts
who m
eet
an in
dic
atio
n f
or
AV
R w
ith
IIa
B
hig
h s
urg
ica
l ris
k
Perc
uta
neous
aort
ic b
allo
on d
ilatio
n m
ay
be c
onsi
dere
d a
s a b
ridge to s
urg
ical o
r tr
ansc
ath
ete
r IIb
C
AV
R in
seve
rely
sym
pto
matic
patie
nts
with
se
vere
AS
TA
VI
is n
ot
reco
mm
ended in
patie
nts
in w
hom
exi
stin
g c
om
orb
iditi
es
wou
ld p
recl
ude t
he e
xpect
ed
III: n
o b
enefit
B
be
ne
fit f
rom
co
rre
ctio
n o
f A
S
AV
R =
aort
ic v
alv
e r
epla
cem
ent, T
AV
I =
tra
nsc
ath
ete
r a
ort
ic v
alv
e im
pla
nta
tion, A
S =
aort
ic s
tenosi
s
33
2.6 Risk factors for associated morbidity and mortality after
surgical AVR
2.6.1 Risk stratification and surgical scores
A predictive score is a statistical algorithm that allows the individual risk of an
event to occur to be assessed before a specific intervention is performed.
Risk models are useful for counseling, decision-making and research
purposes.
Current guidelines recommend the use of risk scores as a useful tool in the
decision process on whether or not to intervene for patients with severe valvular
heart diseases [13].
The ideal risk score should have both good discrimination and calibration.
Discrimination is the ability to differentiate between high- and low-risk patients.
Calibration is the result of the comparison between observed and predicted
outcome.
The European System for Cardiac Operative Risk Evaluation (EuroSCORE II)
and the Society of Thoracic Surgeons (STS) Score are currently the most used
risk scores to predict operative mortality after adult cardiac surgery.
EuroSCORE II is the natural evolution of the Logistic EuroSCORE. It is
derived from a database including 22381 consecutive patients undergoing cardiac
surgery in 154 hospitals of 43 countries during a 12-week observation period
(from May to July 2010). A subsequent validation cohort of 5553 patients was
used for internal validation [31]. It is designed to predict operative mortality and
provide a single percentage independently for the kind of procedure itself. In the
internal validation study, EuroSCORE II provided good discrimination and
calibration [30]. However, an external validation study by Barili and coworkers
has recently demonstrated that EuroSCORE II has a good discrimination but lacks
calibration in high-risk patients [32].
The STS Score is a continuously updated score that is derived from the data
collected from several North American Institutions. The latest version available at
the time of the present thesis is version 2.81. It is designed to predict operative
mortality and morbidity. It provides three different risk models (isolated coronary
5.3 Implantation of Perceval bioprosthesis with minimally invasive
approaches (II)
In this study, 267 patients were included, 189 (70.8%) underwent AVR through
mini-sternotomy and 78 (29.2%) through full sternotomy.
Patients in the two groups had different baseline characteristics. Accordingly,
a propensity score was calculated and used to obtain 56 pairs with similar risk
profile (Table 9).
62
Ta
ble
9. B
as
eli
ne
ch
ara
cte
ris
tic
s o
f p
ati
en
ts w
ho
un
de
rwe
nt
su
ture
les
s A
VR
th
rou
gh
min
iste
rno
tom
y o
r fu
ll s
tern
oto
my.
Variable
s O
vera
ll co
hort
Pro
pensi
ty s
core
cohort
Min
i-st
ern
oto
my
189 p
atie
nts
Full
stern
oto
my
78 p
atie
nts
p
Min
i-st
ern
oto
my
56 p
atie
nts
Full
stern
oto
my
56 p
atie
nts
p
Sta
nd
ard
ize
d
diff
ere
nce
(%
)
Age (
years
) 77.4
±5.1
75.7
±5.5
0.0
16
76.0
±5.6
76.2
±5.0
0.8
40
3.7
Fe
ma
le g
en
de
r 1
16
(6
1)
55
(7
1)
0.1
64
45
(8
0)
42
(7
5)
0.5
33
1
3
Weig
ht (k
g)
74.7
±14.0
74.4
±15.2
0.8
74
73.6
±16.8
74.1
±14.3
0.8
80
3.0
Heig
ht (c
m)
164.2
±10.7
161.1
±7.6
0.0
18
160.6
±14.7
160.8
±7.4
0.9
50
1.1
Dia
be
tes
46
(2
4)
24
(3
1)
0.2
87
17
(3
0)
14
(2
5)
0.5
14
12
Insu
lin-d
ep
en
de
nt
dia
be
tes
12
(6
) 1
2 (
15
) 0
.03
2
8
(1
4)
6 (
11
) 0.5
66
11
Cre
atin
ine c
leara
nce
0.1
62
0.1
98
>8
5 (
ml/m
in)
76
(4
0)
21
(2
7)
12
(2
1)
19
(3
4)
28
50
-85
(m
l/min
) 7
2 (
38
) 3
4 (
44
)
2
5 (
45
) 2
2 (
39
)
11
<5
0 (
ml/m
in)
41
(2
2)
23
(3
0)
19
(3
4)
15
(2
7)
16
New
York
Heart
Ass
oci
atio
n c
lass
0.2
75
0.1
51
I 5
(2
.6)
1 (
1.3
)
2
(3
.6)
1 (
1.8
)
11
II
45
(2
4)
24
(3
1)
24
(4
3)
18
(3
2)
22
III
12
8 (
68
) 4
5 (
58
)
2
5 (
45
) 3
2 (
57
)
25
IV
11
(5
.8)
8 (
10
.3)
5 (
8.9
) 5
(8
.9)
0
Po
or
mo
bili
ty
26
(1
4)
4 (
5.1
) 0
.05
4
2
(3
.6)
3 (
5.3
) 0.6
57
8.6
CC
S c
lass
IV
2
(1
.1)
2 (
2.6
) 0
.58
3
2
(3
.6)
2 (
3.6
) 1.0
0
Co
ron
ary
art
ery
dis
ea
se
7 (
3.7
) 4
(5
.1)
0.7
36
6 (
11
) 2
(3
.6)
0.1
42
28
Chro
nic
pu
lmonary
dis
ease
20 (
11)
18 (
23)
0.0
12
15 (
27)
12 (
21)
0.4
93
12
Ext
raca
rdia
c a
rte
rio
pa
thy
28
(1
5)
19
(2
4)
0.0
77
10
(1
8)
10
(1
8)
1.0
0
Re
cen
t m
yoca
rdia
l in
farc
tion
2
(1
.1)
2 (
2.6
) 0
.58
3
2
(3
.6)
1 (
1.8
) 0.5
71
11
Left v
entr
icula
r eje
ctio
n fra
ctio
n
0.6
96
1.0
>5
0%
1
59
(8
4)
63
(8
1)
48
(8
6)
48
(8
6)
0
30
-50
%
29
(1
5)
14
(1
8)
7 (
13
) 7
(1
3)
0
63
Variable
s O
vera
ll co
hort
Pro
pensi
ty s
core
cohort
Min
i-st
ern
oto
my
189 p
atie
nts
Full
stern
oto
my
78 p
atie
nts
p
Min
i-st
ern
oto
my
56 p
atie
nts
Full
stern
oto
my
56 p
atie
nts
p
Sta
nd
ard
ize
d
diff
ere
nce
(%
)
<3
0%
1
(0
.5)
1 (
1.3
)
1
(1
.8)
1 (
1.8
)
0
Sys
tolic
pulm
onary
art
ery
pre
ssure
0.5
39
0.8
42
31
-55
(m
mH
g)
62
(3
3)
31
(4
0)
22
(3
9)
21
(3
8)
3.7
>5
5 (
mm
Hg
) 2
1 (
11
) 7
(9
.0)
3 (
5.4
) 5
(8
.9)
14
Critic
al p
reo
pera
tive s
tate
0
2 (
2.6
) 0.0
85
0
1 (
1.8
) -
1
9
Ele
ctiv
e p
roce
du
re
18
7 (
99
) 7
2 (
92
) 0
.01
0
5
4 (
96
) 5
4 (
96
) 1.0
0
Pre
vio
us
card
iac
surg
ery
7
(3
.7)
23
(3
0)
<0
.00
1
6
(1
1)
9 (
16
) 0.2
73
16
Pe
rma
ne
nt
pa
cem
ake
r 5
(2
.6)
2 (
2.6
) 1
.0
2
(3
.6)
2 (
3.6
) 1.0
0
Act
ive e
ndoca
rditi
s 0
0
-
0
0
-
-
Eu
roS
CO
RE
II
(%)
3.3
5±2
.86
4
.76
±4
.19
0
.04
4
3
.74
±3
.19
4
.00
±4
.17
0.6
62
7.2
Contin
uou
s va
riab
les
are
report
ed a
s m
ean ±
sta
ndard
devi
atio
n; d
ichoto
mous
variable
s are
report
ed a
s co
un
ts a
nd p
erc
enta
ge
s in
pare
nth
ese
s. D
efin
ition
crite
ria
fo
r p
reo
pe
rativ
e v
aria
ble
s a
re a
cco
rdin
g t
o E
uro
SC
OR
E II. A
VR
= a
ort
ic v
alv
e r
epla
cem
ent, C
AB
G =
coro
nary
art
ery
byp
ass
gra
ftin
g,
CC
S =
Cana
dia
n
Card
iova
scula
r S
oci
ety
.
64
Similar aortic cross-clamping time and cardiopulmonary bypass time were
observed, both in the unmatched and in the matched study populations.
Crystalloid cardioplegia was used more frequently in the mini-sternotomy group
(29% vs. 5.4%, p=0.007) (Table 10).
Similar major outcomes were observed. However, higher transvalvular
gradients were recorded among patients in the mini-sternotomy group (Table 11).
Similar results were observed at 2-year follow-up, both in the unmatched and
in the matched survival analysis (Figure 7 and 8).
65
Ta
ble
10
. O
pe
rati
ve
da
ta o
f p
ati
en
ts w
ho
un
de
rwe
nt
su
ture
les
s A
VR
th
rou
gh
min
iste
rno
tom
y o
r fu
ll s
tern
oto
my.
Variable
s O
vera
ll co
hort
Pro
pensi
ty s
core
cohort
Min
i-st
ern
oto
my
189 p
atie
nts
Full
stern
oto
my
78 p
atie
nts
p
Min
i-st
ern
oto
my
56 p
atie
nts
Full
stern
oto
my
56 p
atie
nts
p
Cry
sta
lloid
ca
rdio
ple
gia
3
1 (
16
) 4
(5
) 0
.01
9
1
6 (
29
) 3
(5
.4)
0.0
07
Hyp
oth
erm
ic c
ircu
lato
ry a
rre
st
0
2 (
2.6
) 0
.08
5
0
1
(1
.8)
-
Perc
eva
l bio
pro
sth
etic
valv
e s
ize
0.0
15
0.6
49
Sm
all
(21
mm
) 1
6 (
8.5
) 1
6 (
21
)
7
(1
2)
11
(2
0)
Me
diu
m (
23
mm
) 7
0 (
37
) 3
0 (
39
)
2
5 (
45
) 2
0 (
36
)
La
rge
(2
5 m
m)
82
(4
3)
29
(3
7)
22
(3
9)
22
(3
9)
Ext
ra la
rge
(2
7 m
m)
21
(1
1)
3 (
3.8
)
2
(3
.6)
3 (
5.4
)
Aort
ic c
ross
-cla
mp
tim
e (
min
) 41±18
43±36
0.5
27
44±23
44±18
0.9
31
Aort
ic c
ross
-cla
mp
tim
e <
30 m
in
45 (
24
) 1
7 (
22
) 0
.87
3
1
7 (
30
) 1
0 (
18
) 0.1
67
Card
iopulm
onary
byp
ass
tim
e (
min
) 70±23
70±24
0.9
79
69±23
74±28
0.3
63
Card
iopulm
onary
byp
ass
tim
e <
60
69 (
37)
31 (
40)
0.6
77
23 (
41)
18 (
32)
0.3
56
Contin
uou
s va
riab
les
are
report
ed a
s m
ean ±
sta
ndard
devi
atio
n; d
ichoto
mous
variable
s are
report
ed a
s co
un
ts a
nd p
erc
enta
ge
s in
pare
nth
ese
s.
66
Ta
ble
11
. P
eri
- a
nd
po
sto
pe
rati
ve
da
ta o
f p
ati
en
ts w
ho
un
de
rwe
nt
su
ture
les
s A
VR
th
rou
gh
min
iste
rno
tom
y o
r fu
ll s
tern
oto
my.
Variable
s O
vera
ll co
hort
Pro
pensi
ty s
core
cohort
Min
i-st
ern
oto
my
189 p
atie
nts
Full
stern
oto
my
78 p
atie
nts
p
Min
i-st
ern
oto
my
56 p
atie
nts
Full
stern
oto
my
56 p
atie
nts
p
Imp
lan
tatio
n s
ucc
ess
1
87
(9
9)
78
(1
00
) 1
.0
5
5 (
98
) 5
6 (
10
0)
-
Re
po
sitio
nin
g o
f p
rost
he
sis
5 (
3.0
) 1
(1
.7)
1.0
2 (
3.6
) 1
(1
.8)
-
Intr
ao
pe
rativ
e p
rost
he
sis
dis
lod
ge
me
nt
1 (
0.5
) 0
-
1
(1
.8)
0
-
Conve
rsio
n to im
pla
nta
tion o
f st
ente
d p
rost
hesi
s 1 (
0.5
) 0
-
0
0
-
Conve
rsio
n t
o f
ull
stern
oto
my
0
0
-
- -
-
Aort
ic v
alv
e P
eak
gra
die
nt (m
mH
g)
28.2
±10.9
25.0
±12.1
0.0
36
28.1
±10.6
23.3
±12.0
0.0
26
Aort
ic v
alv
e M
ean g
radie
nt (m
mH
g)
14.3
±5.9
13.1
±7.0
0.2
15
15.2
±6.1
11.7
±7.0
0.0
11
Para
valv
ula
r re
gurg
itatio
n
0.7
30
-
No
ne
1
84
(9
7)
77
(9
9)
53
(9
5)
56
(1
00
)
Mild
4
(2
.1)
1 (
1.3
)
2
(3
.6)
0
Mo
de
rate
or
seve
re
1 (
0.5
) 0
1
(1
.8)
0
Pack
ed r
ed b
lood c
ells
tra
nsf
usi
ons
(units
) 1.3
5±1.7
1
1.9
9±3.1
5
0.0
34
1.1
5±1.2
4
1.9
1±3.4
9
0.1
28
Str
oke
4
(2
.1)
2 (
2.6
) 1
.0
1
(1
.8)
1 (
1.8
) 1.0
De n
ovo
dia
lysi
s 2 (
1.1
) 4 (
5.1
) 0.0
62
0
2 (
3.6
) -
Pa
cem
ake
r im
pla
nta
tion
1
8 (
9.5
) 4
(5
.2)
0.3
29
6 (
11
) 2
(3
.6)
0.1
78
Re
op
era
tion
for
ea
rly
pa
rava
lvu
lar
reg
urg
itatio
n
1 (
0.5
) 0
-
1
(1
.8)
0
-
Re
op
era
tion
for
ma
jor
ble
ed
ing
8
(4
.2)
4 (
5.1
) 0
.75
1
1
. (1
.8)
3 (
5.4
) 0.3
41
Pro
sthesi
s endo
card
itis
0
0
-
0
0
-
Inte
nsi
ve c
are
unit
stay
(days
) 2.4
±2.3
3.3
±3.5
0.0
53
2.5
±2.8
3.3
±3.8
0.1
55
Hosp
ital s
tay
(days
) 12.2
±5.7
13.4
±10.0
0.3
41
12.5
±6.8
13.4
±10.9
0.5
69
In-h
osp
ital m
ort
alit
y 2
(1
.1)
2 (
2.6
) 0
.58
3
0
2
(3
.6)
-
30
-da
y m
ort
alit
y 1
(0
.5)
0
-
0
0
-
Pro
sth
esi
s-re
late
d e
arly
mo
rta
lity
0
0
-
0
0
-
Contin
uou
s va
riab
les
are
report
ed a
s m
ean ±
sta
ndard
devi
atio
n; d
ichoto
mous
variable
s are
report
ed a
s co
un
ts a
nd p
erc
enta
ge
s in
pare
nth
ese
s.
67
Fig. 7. Kaplan-Meier cumulative survival in the overall cohort (n=267, p=0.423).
Fig. 8. Kaplan-Meier cumulative survival in the propensity score matched cohort
(n=112, p=0.463).
68
5.4 Comparison of minimally invasive Perceval implantation to the
traditional approach with full sternotomy and stented valves (III)
In this study, we investigated the early outcomes and 2-year survival after AVR
performed in 182 patients through a mini-sternotomy with the Perceval sutureless
bioprosthesis compared to 383 patients with a full sternotomy and implantation of
a stented bioprosthesis.Propensity matching resulted in 171 pairs with similar
preoperative risk profiles (Table 12).
69
Ta
ble
12
. B
as
eli
ne
c
ha
rac
teri
sti
cs
fo
r p
ati
en
ts
wh
o
un
de
rwe
nt
ao
rtic
v
alv
e
rep
lac
em
en
t th
rou
gh
a
m
inis
tern
oto
my
w
ith
imp
lan
tati
on
of
a s
utu
rele
ss
bio
pro
sth
es
is o
r th
rou
gh
a f
ull
ste
rno
tom
y w
ith
a s
ten
ted
bio
pro
sth
es
is.
Va
ria
ble
s O
vera
ll co
hort
Pro
pensi
ty s
core
cohort
Min
i-st
ern
oto
my
sutu
rele
ss
189 p
atie
nts
Full
stern
oto
my
Ste
nte
d
383 p
atie
nts
p
Min
i-st
ern
oto
my
sutu
rele
ss
171 p
atie
nts
Full
stern
oto
my
Ste
nte
d
171 p
atie
nts
p
Sta
nd
ard
ize
d
diff
ere
nce
(%
)
Ag
e (
yea
rs)
77.5
±5.2
73.8
±8.2
<
0.0
01
77.3
± 5
.1
77.4
± 6
.1
0.9
23
-0
.9
Fem
ale
gender
11
2 (
62
) 1
72
(4
5)
<0
.00
1
1
02
(6
0)
10
8 (
63
) 0
.51
3
-7.2
Weig
ht (k
g)
74.5
±14
76.8
±16
0.0
88
74.8
±14
74.7
±15
0.9
45
0.7
Heig
ht (c
m)
164±11
160±40
0.0
58
165±11
159±36
0.0
72
21
Body
mass
inde
x (k
g/m
2)
27.3
±4.4
26.5
±4.5
0.0
58
27.3
±4.4
26.7
±4.7
0.2
68
11
Dia
bete
s m
elli
tus
43
(2
4)
55
(1
4)
0.0
09
38
(2
2)
31
(1
8)
0.3
09
10
Insu
lin-d
epe
ndent
21
(5
.5)
21
(5
.5)
0.8
46
10
(5
.9)
7 (
4.1
) 0.4
69
8.1
Cre
atin
ine c
leara
nce
<
0.0
01
0.8
23
>85 (
ml/m
in)
37
(2
0)
82
(2
2)
67
(4
0)
69
(3
9)
2.4
50
-85
(m
l/min
) 6
7 (
37
) 2
03
(5
4)
66
(3
9)
71
(4
2)
-6.0
<50 (
ml/m
in)
78
(4
3)
94
(2
5)
36
(2
1)
33
(1
9)
4.4
Coro
nary
art
ery
dis
ease
3
(1
.6)
22
(5
.7)
0.0
28
3 (
1.8
) 3
(1
.8)
1
0
Rece
nt m
yoca
rdia
l infa
rctio
n
2 (
1.1
) 1
1 (
2.9
) 0
.24
0
2
(1
.2)
3 (
1.8
) 0.6
57
-4
.9
Chro
nic
pu
lmonary
dis
ease
2
0 (
11
.0)
27
(7
.0)
0.1
41
15
(8
.8)
15
(8
.8)
1
0
Ext
raca
rdia
c a
rte
rio
pa
thy
25
(1
3.7
) 3
3 (
8.7
) 0
.07
5
2
2 (
13
) 2
0 (
12
) 0.7
15
3.6
Left v
entr
icula
r eje
ctio
n fra
ctio
n
0.0
64
0.8
84
>50%
1
52
(8
4)
29
7 (
79
)
1
43
(8
4)
14
2 (
83
)
1.6
30
-50
%
29
(1
6)
65
(1
7)
28
(1
6)
29
(1
7)
-1.6
<30%
1
(0
.5)
15
(4
.0)
0
0
-
-
Non-e
lect
ive p
roce
dure
2
(1
.1)
29
(7
.6)
0.0
02
2(1
.2)
3(1
.8)
0.6
57
-4
.9
Lo
gis
tic E
uro
SC
OR
E I
(%
) 7.7
±0.3
10.6
±0.6
<
0.0
01
9.8
±5.5
9.6
±6.9
0.7
01
3.6
Contin
uou
s va
riab
les
are
report
ed a
s m
ean ±
sta
ndard
devi
atio
n; d
ichoto
mous
variable
s are
report
ed a
s co
un
ts a
nd p
erc
enta
ge
s in
pare
nth
ese
s.
70
When operative details were considered, the use of the Perceval sutureless
prosthesis was associated with significantly shorter cross-clamping and
cardiopulmonary bypass times (Table 13).
71
Ta
ble
13
. A
ort
ic c
ros
s-c
lam
p a
nd
ca
rdio
pu
lmo
na
ry b
yp
as
s t
ime
fo
r p
ati
en
ts w
ho
un
de
rwe
nt
ao
rtic
va
lve r
ep
lace
me
nt
thro
ug
h a
min
iste
rno
tom
y w
ith
im
pla
nta
tio
n o
f a
su
ture
les
s b
iop
rosth
es
is o
r th
rou
gh
a f
ull s
tern
oto
my
wit
h a
ste
nte
d b
iop
rosth
esis
.
Variable
s O
vera
ll co
hort
Pro
pensi
ty s
core
cohort
Min
i-st
ern
oto
my
sutu
rele
ss
189 p
atie
nts
Full
stern
oto
my
Ste
nte
d
383 p
atie
nts
p
Min
i-st
ern
oto
my
sutu
rele
ss
171 p
atie
nts
Full
stern
oto
my
Ste
nte
d
171 p
atie
nts
p
Aort
ic c
ross
-cla
mp
tim
e (
min
) 41±17
65±15
<
0.0
01
40±15
65±15
<
0.0
01
Aort
ic c
ross
-cla
mp
tim
e <
30 m
in
45 (
25)
0
<0.0
01
43 (
25)
0
<0.0
01
Card
iopulm
onary
byp
ass
tim
e (
min
) 69±23
86±20
<
0.0
01
69±20
87±20
<
0.0
01
Card
iopulm
onary
byp
ass
tim
e <
60
69 (
38)
19 (
5.0
) <
0.0
01
65 (
38)
6 (
3.5
) <
0.0
01
Contin
uou
s va
riab
les
are
report
ed a
s m
ean ±
sta
ndard
devi
atio
n; d
ichoto
mous
variable
s are
report
ed a
s co
un
ts a
nd p
erc
enta
ge
s in
pare
nth
ese
s.
72
Operative mortality in the propensity-matched cohort was 1.8% in the mini-
sternotomy sutureless group and 2.3% in the full sternotomy stented group
(p=0.706).
Patients in the mini-sternotomy sutureless group required more frequent
implantation of permanent pacemaker (9.9 vs. 2.9%, p=0.016) but fewer
transfusions of packed red blood cells (1.4 vs. 2.4 units, p<0.001) (Table 14).
73
Ta
ble
14
. P
os
top
era
tiv
e d
ata
fo
r p
ati
en
ts w
ho
un
de
rwen
t ao
rtic
valv
e r
ep
lac
em
en
t th
rou
gh
a m
inis
tern
oto
my
wit
h i
mp
lan
tati
on
of
a s
utu
rele
ss
bio
pro
sth
es
is o
r th
rou
gh
a f
ull
ste
rno
tom
y w
ith
a s
ten
ted
bio
pro
sth
es
is.
Variable
s O
vera
ll co
hort
Pro
pensi
ty s
core
cohort
Min
i-st
ern
oto
my
sutu
rele
ss
189 p
atie
nts
Full
stern
oto
my
Ste
nte
d
383 p
atie
nts
p
Min
i-st
ern
oto
my
sutu
rele
ss
171 p
atie
nts
Full
stern
oto
my
Ste
nte
d
171 p
atie
nts
p
Para
valv
ula
r re
gurg
itatio
n
0.3
81
0.4
84
No
ne
1
78
(9
8)
37
0 (
97
)
1
67
(9
8)
16
5 (
96
)
Mild
4
(2
.2)
9 (
2.3
)
4
(2
.3)
4 (
2.3
)
Mo
de
rate
or
seve
re
0
4 (
1.0
)
0
2
(1
.2)
Pack
ed r
ed b
lood c
ells
tra
nsf
usi
ons
(units
) 1.4
±1.7
2.6
±4.5
<
0.0
01
1.4
±1.7
2.4
±2.7
<
0.0
01
Str
oke
4
(2
.2)
2 (
0.5
) 0
.08
8
4
(2
.3)
2 (
1.2
) 0.4
23
De
no
vo d
ialy
sis
2 (
1.1
) 1
0 (
2.6
) 0
.35
4
2
(1
.2)
3 (
1.8
) 0.6
57
Pa
cem
ake
r im
pla
nta
tion
1
7 (
9.3
) 7
(1
.8)
<0
.00
1
1
7 (
9.9
) 5
(2
.9)
0.0
16
Re
op
era
tion
for
ea
rly
pa
rava
lvu
lar
reg
urg
itatio
n
0
1 (
0.3
) 1
0
0
-
Re
op
era
tion
for
ma
jor
ble
ed
ing
8
(4
.4)
30
(7
.8)
0.1
52
7 (
4.1
) 1
1 (
6.4
) 0.3
23
Inte
nsi
ve c
are
unit
stay
(days
) 2.4
±2.3
1.6
±2.8
<
0.0
01
2.5
±2.3
1.9
±2.9
0.0
54
30
-da
y m
ort
alit
y 3
(1
.6)
8 (
2.1
) 1
3 (
1.8
) 4
(2
.3)
0.7
06
Contin
uou
s va
riab
les
are
report
ed a
s m
ean ±
sta
ndard
devi
atio
n; d
ichoto
mous
variable
s are
report
ed a
s co
un
ts a
nd p
erc
enta
ge
s in
pare
nth
ese
s.
74
Two-year survival was similar between the two groups in the unmatched
(mini-sternotomy 92.0% vs full sternotomy 92.4%, p=0.90) (Figure 9) and in the
matched analysis (mini-sternotomy91.0% vs full sternotomy 93.0%,
p=0.90)(Figure 10).
75
Fig. 9. Kaplan-Meier cumulative survival in the overall cohort (n=565, p=0.669). (FS =
full sternotomy; MS = ministernotomy).
Fig. 10. Kaplan-Meier cumulative survival in the propensity score matched cohort
(n=342, p=0.895). (FS = full sternotomy; MS = ministernotomy).
76
5.5 In-hospital outcomes and 1-year survival after AVR with the
Perceval sutureless bioprosthesis vs TAVI (IV)
TAVI is no longer an emerging technology for the treatment of severe
symptomatic aortic stenosis. Excellent results have been reported in inoperable or
high-risk patients. However, in study I we demonstrated that the observed
mortality was significantly lower than predicted when the Perceval sutureless
bioprosthesis was employed. Accordingly, the Perceval sutureless bioprosthesis
may further enhance surgical indications also for patients at high-risk. Therefore,
in this study we compared data of 292 patients receiving the Perceval sutureless
bioprosthesis from our multicenter European registry to those of 1885 patients
treated with the balloon expandable Sapien and Sapien XT bioprostheses
(Edwards Lifesciences, Irvine, CA, USA) from the Italian Transcatheter balloon
Expandable Registry – ITER.
In order to overcome significant differences in preoperative risk profiles,
three different propensity score matching procedures have been performed (Table
15).
Table 15. Postoperative data on patients who underwent AVR with the Perceval
sutureless bioprosthesis.
Variables Matching Sutureless TAVI p
Age Before matching a 76.8±5 81.7±6 <0.01
After individual matching b 77.4±5.4 77.7±7.9 0.08
After matching in TA c 78.3±5.3 78.5±8.7 0.18
After matching in TF d 77.7±5.0 77.7±7.0 0.57
Female gender Before matching a 188(64.4) 1139(60.4) 0.20
After individual matching b 138 (64.5) 139 (65.0) 0.92
After matching in TA c 69 (65.7) 69 (65.7) >0.99
After matching in TF d 139 (68.0) 131 (64.0) 0.41
Body Mass Index Before matching a 27.7±4.7 25.8±4.5 <0.01
After individual matching b 27.5±4.7 27.6±5.2 0.99
After matching in TA c 26.9±4.6 26.8±4.8 0.76
After matching in TF d 27.5±4.6 27.7±5.5 0.93
Diabetes Before matching a 77(26.4) 483(25.6) 0.79
After individual matching b 59 (27.6) 58 (27.1) 0.91
After matching in TA c 27 (25.7) 28 (26.7) 0.88
After matching in TF d 55 (26.7) 56 (27.2) 0.91
Extracardiac arteriopathy Before matching a 50(17.1) 657(34.9) <0.01
After individual matching b 46 (21.5) 48 (22.4) 0.82
After matching in TA c 33 (31.4) 37 (35.2) 0.56
77
Variables Matching Sutureless TAVI p
After matching in TF d 38 (18.5) 38 (18.5) >0.99
Chronic lung disease Before matching a 41(14.0) 462(24.5) <0.01
After individual matching b 39 (18.2) 36 (16.8) 0.70
After matching in TA c 20 (19.1) 20 (19.1) >0.99
After matching in TF d 36 (17.5) 38 (18.5) 0.80
Previous cardiac surgery Before matching a 29(9.9) 348(18.5) <0.01
After individual matching b 22 (10.3) 21 (9.8) 0.87
After matching in TA c 15 (14.3) 12 (11.4) 0.54
After matching in TF d 19 (9.2) 22 (10.7) 0.62
Renal impairment Before matching a <0.01
>85 ml/min 107 (36.6) 97 (5.2)
84-51 ml/min 111 (40.1) 618 (33.2)
≤50 ml/min 67 (23) 1090 (58.5)
dialysis 1 (0.3) 59 (3.2)
After individual matching b 0.97
>85 ml/min 46 (21.5) 42 (19.6)
84-51 ml/min 101 (47.2) 102(47.6)
≤50 ml/min 66 (30.8) 69 (32.2)
dialysis 1 (0.5) 1 (0.5)
After matching in TA c 0.66
>85 ml/min 10 (9.5) 12 (11.4)
84-51 ml/min 45 (42.9) 49 (46.7)
≤50 ml/min 66 (32.0) 44 (41.9)
dialysis 1 (0.5) 0
After matching in TF d 0.70
>85 ml/min 45 (21.8) 40 (19.4)
84-51 ml/min 94 (45.6) 104 (50.5)
≤50 ml/min 66 (32.0) 60 (29.1)
dialysis 1 (0.5) 2 (1.0)
Pulmonary hypertension Before matching a <0.01
No 246 (84.3) 742 (39.4)
31-55 mmHg 45 (15.4) 939 (49.8)
>55 mmHg 1 (0.3) 204 (10.8)
After individual matching b 0.60
No 168 (78.5) 170 (79.4)
31-55 mmHg 45 (21.0) 44 (20.6)
>55 mmHg 1 (0.5) 1 (0.5)
After matching in TA c 0.65
No 71 (67.6) 75 (71.4)
31-55 mmHg 33 (31.4) 28 (26.7)
>55 mmHg 1 (1.0) 2 (1.9)
After matching in TF d 0.57
78
Variables Matching Sutureless TAVI p
No 160 (77.7) 158 (76.7)
31-55 mmHg 45 (21.8) 48 (23.3)
>55 mmHg 1 (0.5) 0
Hystory of CAD Before matching a 12 (4.1) 767 (40.7) <0.01
After matching b 12 (5.6) 11 (5.1) 0.83
After matching in TA c 12 (11.4) 15 (14.3) 0.54
After matching in TF d 12 (5.8) 15 (7.3) 0.55
LVEF Before matching a 58.4±9.0 53.6±12.3 <0.01
After matching b 57.7±9.3 58.2±10.2 0.41
After matching in TA c 57.3±10.6 57.3±11.2 0.88
After matching in TF d 57.6±9.3 57.7±9.5 0.82
Only variables with less than 1% missing values were included in the analysis. Data are expressed in
numbers (percentage) or mean ± standard deviation. a There were 292 patients for the Sutureless treated group and 1885 patients for the TAVI treated group b There were 214 patients for the Sutureless treated group and 214 patients for the TAVI treated group
c There were 105 patients for the Sutureless treated group and 105 patients for the TAVI treated group d There were 206 patients for the Sutureless treated group and 206 patients for the TAVI treated group
Comparisons between groups are made using the Wilcoxon-Mann-Whitney test.
The only significant difference was found in terms of mild PVL, which was
higher in transapical TAVI patients (36.1% vs. 2.9%, p<0.01), but not severe PVL
(1.0% vs. 1.0%, p=1.00). The Perceval study grouphad higher transvalvular
gradients and longer intensive care unit andin-hospital length of stay (Table 16).
5.5.3 Perceval sutureless bioprosthesis vs trans-femoral TAVI
Transfemoral TAVI patients had a lower rate of device success (85.9 vs. 98.1%,
p<0.01) when compared to AVR with the Perceval sutureless bioprosthesis.
Furthermore, in the transfemoral TAVI cohort we observed a higher incidence
of severe (6.3% vs. 0.5%, p=0.01) as well as any PVL (33.5 vs. 3.4 %; p<0.01).
There were no significant differences between groups in terms of 30-day and one-
yearmortality, stroke, bleeding, PM implantation and myocardial infarction.The
Perceval study group had higher transvalvular gradients and longer intensive care
unit and in-hospital length of stay (Table 16).
Table 16. Postoperative data on patients who underwent AVR with the Perceval
sutureless bioprosthesis.
Variables Matching Sutureless TAVI p
30-day mortality Before matching a 6 (2) 134 (7) <0.01
After individual matching b 5 (2.3) 8 (3.7) 0.401
After matching in TA c 3 (2.9) 4 (3.8) >0.99
After matching in TF d 5 (2.4) 9 (4.4) 0.28
1-year mortality Before matching a 13 (4.6) 7miss 242 (12.9)7miss <0.01
After individual matching b 12 (5.8) 6 miss 20 (9.4) 1 miss 0.16
After matching in TA c 8 (8.0) 5 miss 11 (10.5) 0.54
After matching in TF d 12 (6.0) 6 miss 15 (7.4) 2 miss 0.59
Device success Before matching a 288 (98.6) 1661 (88.1) <0.01
After individual matching b 211 (98.6) 190 (88.8) <0.01
After matching in TA c 103 (98.1) 99 (94.3) 0.28
After matching in TF d 202 (98.1) 177 (85.9) <0.01
Any stroke Before matching a 6 (2.1) 52 (2.8) 0.49
After individual matching b 4 (1.9) 4 (1.9) >0.99
After matching in TA c 2 (1.9) 1 (1.0) >0.99
After matching in TF d 2 (1.0) 3 (1.5) >0.99
Bleeding (life-threatening or
major)
Before matching a 44 (15.1) 381 (20.4) 0.03
After individual matching b 40 (18.7) 34 (16.1) 0.48
After matching in TA c 21 (20.0) 13 (13.0) 0.18
After matching in TF d 39 (19.0) 32 (15.0) 0.36
Permanent PM implantation Before matching a 26 (8.9) 116 (6.2) 0.08
80
Variables Matching Sutureless TAVI p
After individual matching b 20 (9.4) 6 (2.8) 0.01
After matching in TA c 10 (9.5) 4 (3.8) 0.10
After matching in TF d 19 (9.2) 12 (5.8) 0.19
Any myocardial infarction Before matching a 1 (0.3) 28 (1.5) 0.17
After individual matching b 1 (0.5) 2 (0.9) >0.99
After matching in TA c 1 (1.0) 2 (1.9) >0.99
After matching in TF d 1 (0.5) 1 (0.5) >0.99
Severe paravalvular leak Before matching a 1 (0.3) 98 (5.2) <0.01
After individual matching b 1 (0.5) 11 (5.1) 0.06
After matching in TA c 1 (1.0) 1 (1.0) >0.99
After matching in TF d 1 (0.5) 13 (6.3) <0.01
Any paravalvular leak Before matching a <0.01
No 268 (98.0) 1125 (62.7)
Mild 5 (1.7) 571 (31.8)
>Mild 1 (0.3) 98 (5.5)
After individual matching b <0.01
No 208 (97.2) 134 (64.7)
Mild 5 (2.3) 62 (30.0)
>Mild 1 (0.5) 11 (5.3)
After matching in TA c <0.01
No 101 (96.1) 66 (62.9)
Mild 3 (2.9) 38 (36.1)
>Mild 1 (1.0) 1 (1.0)
After matching in TF d <0.01
No 199 (96.6) 137(66.5)
Mild 5 (2.4) 56 (27.2)
>Mild 2 (1.0) 13 (6.3
Data are expressed in number (percentage) aThere were 292 patients for the SL treated group and 1885 patients for the TAVI treated group b There were 214 patients for the SL treated group and 214 patients for the TAVI treated group c There were 105 patients for the SL treated group and 105 patients for the TAVI treated group d There were 206 patients for the SL treated group and 206 patients for the TAVI treated group
Comparisons between groups are made using the Wilcoxon-Mann-Whitney test.
VARC = Valve academic research consortium, TAVI = Trans-catheter aortic valve implantation, TA =
Trans-apical, TF = Trans-femoral, PM = Pacemaker, miss = missing
5.6 Immediate outcomes after AVR with the Perceval sutureless
bioprosthesisvs TAVI (V)
We compared 379 patients who underwent AVR with the Perceval sutureless
bioprosthesiswith 394 patients treated with TAVI. Patients in both groups differed
81
in a number of baseline characteristics. In particular, 25.6% of patients in the
Perceval study group underwent concomitant CABG, whereas PCI was
performed only in 2.0% of TAVI patients (Table 17 and Figure 11). Unfortunately,
details on coronary disease and pattern were not available in the interventional
arm of the study, since current practice privileges TAVI alone in patients with
coronary artery disease, since the value of concomitant PCI is still controversial
[50]. Therefore, any coronary procedure in both groups was not considered for
the calculation of the propensity score.
Fig. 11. Distribution of patients to TAVI and sutureless aortic valve replacement (SU-
AVR) groups according to EuroSCORE II values.
82
Ta
ble
17
. B
as
eli
ne c
ha
rac
teri
sti
cs o
f p
ati
en
ts w
ho
un
de
rwe
nt
tran
sc
ath
ete
r (T
AV
I) v
ers
us
su
rgic
al
ao
rtic
valv
e r
ep
lac
em
en
t w
ith
Pe
rce
va
l s
utu
rele
ss
bio
pro
sth
es
is.
Variable
s O
vera
ll co
hort
25
th-7
5th p
erc
en
tile
of
ES
II
P
rop
en
sity
-ma
tch
ed
pa
irs
Su
ture
less
379 p
atie
nts
TA
VI
394 p
atie
nts
p
Sutu
rele
ss
180 p
atie
nts
TA
VI
180 p
atie
nts
p
Sutu
rele
ss
144 p
atie
nts
TA
VI
144 p
atie
nts
p
Age (
years
) 77.4
±5.4
80.8
±5.5
<
0.0
001
78.9
±5.3
81.5
±4.9
<
0.0
001
79.4
±5.4
79.0
±6.0
0.7
45
Fe
ma
les
23
6 (
62
.3)
22
9 (
58
.1)
0.2
39
11
3 (
62
.8)
13
5 (
64
.6)
0.7
10
88
(6
1.1
) 9
0 (
62
.5)
0.8
08
Insu
lin-d
ep
en
de
nt
dia
be
tes
37
(9
.8)
11
(2
.8)
<0
.00
01
1
6 (
8.9
) 5
(2
.4)
0.0
05
6 (
4.2
) 5
(3
.5)
0.7
59
Cre
atin
ine c
leara
nce
<
0.0
001
<
0.0
001
0.4
76
50
-85
ml/m
in
15
0 (
39
.6)
15
8 (
40
.1)
75
(4
1.7
) 9
1 (
43
.5)
67
(4
6.5
) 7
3 (
50
.7)
<5
0 m
l/min
8
5 (
22
.4)
20
3 (
51
.5)
44
(2
4.4
) 1
09
(5
2.2
)
4
6 (
31
.9)
48
(3
3.3
)
New
York
Heart
Ass
oci
atio
n c
lass
0.6
55
0.7
79
0.6
10
III
25
5 (
67
.3)
26
4 (
67
.0)
12
9 (
71
.7)
14
1 (
67
.5)
10
1 (
70
.1)
94
(6
5.3
)
IV
24
(6
.3)
30
(7
.6)
11
(6
.1)
12
(5
.7)
7 (
4.9
) 1
1 (
7.6
)
CC
S c
lass
IV
1
2 (
3.2
) 4
6 (
11
.7)
<
0.0
00
1
3 (
1.7
) 1
7 (
8.1
) 0
.00
5
6
(4
.2)
6 (
4.2
) 1
.00
0
Pu
lmo
na
ry d
ise
ase
6
3 (
16
.6)
13
6 (
34
.5)
<0
.00
01
3
5 (
19
.4)
67
(3
2.1
) 0
.00
5
3
8 (
26
.4)
35
(2
4.3
) 0
.68
4
Ext
raca
rdia
c a
rte
rio
pa
thy
83
(2
1.9
) 2
7 (
6.9
) <
0.0
00
1
43
(2
3.9
) 7
(3
.3)
<0
.00
01
1
2 (
8.3
) 1
3 (
9.0
) 0
.83
4
Re
cen
t m
yoca
rdia
l in
farc
tion
6
(1
.6)
68
(1
7.3
) <
0.0
00
1
3 (
1.7
) 2
4 (
11
.5)
<0
.00
01
5
(3
.5)
3 (
2.1
) 0
.72
3
Left v
entr
icula
r eje
ctio
n fra
ctio
n
<0.0
001
0.2
25
0.7
98
31
-50
%
57
(1
5.0
) 1
00
(2
5.4
)
2
8 (
15
.6)
41
(1
9.6
)
2
6 (
18
.1)
23
(1
6.0
)
21
-30
%
3 (
0.8
) 2
3 (
5.8
)
1
(0
.6)
5 (
2.4
)
3
(2
.1)
2 (
1.2
)
≤20
%
0
5 (
1.3
)
0
(0
) 1
(0
.5)
0 (
0)
0 (
0)
Sys
tolic
pulm
onary
art
erial p
ress
ure
<
0.0
001
<
0.0
001
0.9
83
31
-55
mm
Hg
1
40
(3
6.9
) 2
56
(6
5.0
)
7
3 (
40
.6)
14
8 (
70
.8)
75
(5
2.1
) 7
4 (
51
.4)
>5
5 m
mH
g
37
(9
.8)
51
(1
2.9
)
2
0 (
11
.1)
22
(1
0.5
)
1
7 (
11
.8)
18
(1
2.5
)
83
Variable
s O
vera
ll co
hort
25
th-7
5th p
erc
en
tile
of
ES
II
P
rop
en
sity
-ma
tch
ed
pa
irs
Su
ture
less
379 p
atie
nts
TA
VI
394 p
atie
nts
p
Sutu
rele
ss
180 p
atie
nts
TA
VI
180 p
atie
nts
p
Sutu
rele
ss
144 p
atie
nts
TA
VI
144 p
atie
nts
p
Critic
al p
reo
pe
rativ
e s
tate
3
(0
.8)
0
0.1
17
1 (
0.6
) 0
(0
) 0
.46
3
0
(0
) 0
(0
) -
Ele
ctiv
e p
roce
du
re
36
3 (
95
.8)
39
4 (
10
0)
<0
.00
01
1
76
(9
7.8
) 2
09
(1
00
) 0
.03
0
1
44
(1
00
) 1
44
(1
00
) -
Pre
vio
us
card
iac
surg
ery
3
3 (
8.7
) 6
0 (
15
.2)
0.0
05
13
(7
.2)
5 (
2.4
) 0
.02
9
1
2 (
8.3
) 1
5 (
10
.4)
0.5
44
Ao
rtic
va
lve
su
rge
ry
12
(3
.2)
9 (
2.3
) 0
.51
1
3
(1
.7)
0 (
0)
0.0
98
6 (
4.2
) 4
(2
.8)
0.5
20
Pe
rma
ne
nt
pa
ce-m
ake
r 1
0 (
2.6
) 3
5 (
8.9
) <
0.0
00
1
6 (
3.3
) 1
0 (
4.8
) 0
.47
2
7
(4
.9)
7 (
4.9
) 1
.00
0
Eu
roS
CO
RE
II
(%)
4.0
±3
.9
5.6
±4
.9
<0
.00
01
3
.4±1
.0
3.7
±1
.1
0.0
02
4.1
±3.2
3.6
±2.6
0.1
17
Contin
uou
s va
riab
les
are
report
ed a
s m
ean ±
sta
ndard
devi
atio
n; d
ichoto
mous
variable
s are
report
ed a
s co
un
ts a
nd p
erc
enta
ge
s in
pare
nth
ese
s; D
efin
ition
crite
ria f
or
pre
opera
tive v
ariab
les
are
acc
ord
ing
to
Eu
roS
CO
RE
II,
ES
= E
uro
SC
OR
E I
I.
84
In the unmatched population, we observed that TAVI was associated with an
increased risk of moderate-to-severe PVL and need for permanent pacemaker
implantation. Conversely, sutureless prostheses had a greater incidence of device
failure, because postprocedural echocardiography showed a mean gradient ≥20
mmHg in 16.1% of surgical patients (16.1% vs. 2.3%, p<0.0001). TAVI showed a
slight trend toward operative mortality, although it was not statistically significant
(2.6% after vs 5.3%, p=0.057) (Table 18).
Analyses including patients comprised between the 25th and 75th percentiles
of EuroSCORE II confirmed the previous findings, but we observed similar
trends for permanent pacemaker implantation (Table 18).
Propensity matching generated 144 pairs with similar preoperative risk
profiles. Operative mortality was significantly lower in the Perceval study group
(1.4% vs. 6.9%, p=0.035). TAVI was associated with a greater incidence of
vascular complication and the occurrence of PVL, whereas patients in the
Perceval study group had an increased risk of reoperation for major bleeding
(Table 18).
85
Ta
ble
18
. Im
med
iate
po
sto
pe
rati
ve
data
on
pati
en
ts w
ho
un
de
rwen
t tr
an
sc
ath
ete
r (T
AV
I) a
nd
su
rgic
al
ao
rtic
valv
e r
ep
lac
em
en
t
wit
h P
erc
ev
al
su
ture
les
s b
iop
ros
the
sis
.
Variable
s O
vera
ll co
hort
25
th-7
5th p
erc
en
tile
of
ES
II
P
rop
en
sity
-ma
tch
ed
pa
irs
Su
ture
less
379 p
atie
nts
TA
VI
394 p
atie
nts
p
Sutu
rele
ss
180 p
atie
nts
TA
VI
180 p
atie
nts
p
Sutu
rele
ss
144 p
atie
nts
TA
VI
144 p
atie
nts
p
Devi
ce s
ucc
ess
305 (
80.5
) 309 (
78.4
) 0.4
81
146 (
81.1
) 168 (
80.4
) 0
.85
6
1
15
(7
9.9
) 1
12
(7
7.8
) 0
.66
5
Valv
ula
r re
gurg
itatio
n
<0.0
001
<
0.0
001
<0.0
001
No
ne
3
70
(9
7.6
) 1
63
(4
1.9
)
1
74
(9
6.7
) 9
3 (
44
.7)
14
0 (
97
.2)
66
(4
6.5
)
Mild
8
(2
.1)
17
1 (
44
.0)
5 (
2.8
) 8
8 (
42
.3)
3 (
2.1
) 5
5 (
38
.7)
Mo
de
rate
- se
vere
1
(0
.3)
55
(1
4.1
)
1
(0
.6)
27
(1
3.0
)
1
(0
.7)
21
(1
4.8
)
Co
nve
rsio
n t
o c
on
ven
tion
al A
VR
2
(0
.5)
0 (
0)
0.2
40
1 (
0.6
) 0
(0
) 0
.46
3
0
(0
) 0
(0
) -
Str
oke
9
(2
.4)
5 (
1.3
) 0
.25
1
2
(1
.1)
2 (
1.0
) 1
.00
0
0
(0
) 3
(2
.1)
0.1
22
De
no
vo d
ialy
sis
11
(2
.9)
3 (
0.8
) 0
.03
1
5
(2
.8)
1 (
0.5
) 0
.10
0
3
(2
.1)
0 (
0)
0.2
47
Pa
ce-m
ake
r im
pla
nta
tion
3
7 (
9.8
) 6
8 (
17
.3)
0.0
03
20
(1
1.0
) 3
5 (
16
.8)
0.1
12
16
(1
1.2
) 2
2 (
15
.4)
0.2
96
Vasc
ula
r acc
ess
com
plic
atio
n
0 (
0)
45 (
11.4
) <
0.0
001
0 (
0)
28 (
13.4
) <
0.0
001
0 (
0)
15 (
10.4
) <
0.0
001
Re
op
era
tion
for
ma
jor
ble
ed
ing
1
4 (
3.7
) 0
(0
) <
0.0
00
1
9 (
5.0
) 0
(0
) 0
.00
1
6
(4
.2)
0 (
0)
0.0
13
In-h
osp
ital m
ort
alit
y 1
0 (
2.6
) 2
1 (
5.3
) 0
.05
7
2
(1
.1)
8 (
3.8
) 0
.11
5
2
(1
.4)
10
(6
.9)
0.0
35
Contin
uou
s va
riab
les
are
report
ed a
s m
ean ±
sta
ndard
devi
atio
n; d
ichoto
mous
variable
s are
report
ed a
s co
un
ts a
nd p
erc
enta
ge
s in
pa
ren
the
ses.
ES
=
Eu
roS
CO
RE
II.
86
5.7 Hemodynamic assessment of the Perceval sutureless
bioprosthesis with dobutamine stress echocardiography (VI)
Baseline characteristics and detail of size of the prosthesis are shown in Table 19.
Table 19. Baseline characteristics, preoperative echocardiographic details and size of
implanted valves.
Variables n=32
Age at surgery (years) 74.6±5.6
Gender (F) 18 (56.3%)
Height (m) 160.7±8.1
Weight (Kg) 70.1±13.3
Body surface area (m2) 1.76±0.18
Body mass index (Kg/m2) 27.2±5.2
eGFR classes
>85 ml/min/m2 3 (9.4%)
50-85 ml/min/m2 21 (65.6%)
<50 ml/min/m2 8 (25%)
Extracardiac arteriopathy 4 (12.5%)
Poor mobility 1 (3.1%)
Redo 2 (6.3%)
Chronic lung disease 5 (15.6%)
IDDM 6 (18.8%)
NYHA III-IV 24 (75%)
LVEF 57.3±8.1%
LVEF classes
>50% 25 (78.1%)
30-50% 7 (21.9%)
PAPs (mmHg) 31.9±7.9
PAPs classes
<30 mmHg 15 (46.9%)
31-55 mmHg 17 (53.1%)
EuroSCORE II 4.16±3.47%
Annulus (mm) 22.2±1.8
Sinuses of Valsalva (mm) 30.0±2.9
Sino-tubular junction (mm) 26.6±2.3
Aortic root height (mm) 17.7±2.6
Peak gradient (mmHg) 81.0±24.1
Mean gradient (mmHg) 48.6±18.0
AVA (cm2) 0.7±0.2
AVAi (cm2/m2) 0.38±0.15
Full sternotomy 18 (52.2%)
87
Variables n=32
J mini-sternotomy 14 (43.8%)
Size
S 10 (31.3%)
M 9 (28.1%)
L 8 (25%)
XL 5 (15.6%)
AVA(i) = aortic valve area (index)
Gradients and valve area at discharge significantly improved compared to
preoperative values, and remained stable after a median follow-up of 19.5 months
(IQR 15.3-27.3) (Table 20). However, 8 patients (25%) showed severe PPM.
Table 20. Variation of transvalvular gradients and valve areas from preoperative
values to follow-up.
Variables Preoperative Discharge Follow-up
Peak gradient 81.0±24.1 22.9±9.4*** 24.0±7.6NS
Mean gradient 48.6±18.0 12.6±5.5*** 12.6±4.2 NS
AVA 0.7±0.2 1.5±0.2*** 1.5±0.5 NS
AVAi 0.38±0.15 0.85±0.14*** 0.84±0.26 NS
AVA(i) = aortic valve area (index). *** = p<0.001 vs preoperative, NS = p not significant vs discharge
All patients completed the DSE test without complications. We have observed a
significant increase of transvalvular gradients, EOA, EOAi and DVI.
Mean percentage increase of EOAi was 40.3±28.0% (Table 21).
Table 21. Hemodynamic assessments during dobutamine stress echocardiography.
Variables Rest Exercise p
Heart rate 71.0±10.5 119.0±11.0 <0.001
Stroke volume (ml) 69.1±14.2 90.1±17.1 <0.001
LVEF (%) 57.6±7.4 62.8±7.5 <0.001
Peak gradient 24.0±7.6 38.7±13.6 <0.001
Mean gradient 12.6±4.2 19.8±8.3 <0.001
EOA 1.5±0.5 2.1±0.7 <0.001
EOAi 0.84±0.26 1.17±0.37 <0.001
DVI 0.47±0.13 0.66±0.20 <0.001
Severe PPM 8 (25%) 1 (3.1%) <0.001
LVEF = left ventricular ejection fraction, EOA(i) = effective orifice area (index), DVI = dimensionless
However, other major investigated outcomes were similar between groups
(stroke, de novo dialysis, conversion to conventional AVR). It is interesting to
note that the main observed differences were coherent with the different technical
procedures.
Accordingly, surgery was associated with a greater increase of postoperative
bleeding requiring reoperation, whereas vascular access complications were more
frequently observed in TAVI patients. Similarly, different etiologies were
responsible for the observed freedom from immediate device success (PVL in the
TAVI cohort, higher gradients in the Perceval cohort). This study further confirms
that the two techniques are completely different, either from a procedural or
outcome point of view. This has been already highlighted by other institutional
reports as well as in our previous Study IV [145–147].However, future
improvement in valve profile as well as in technical devices that will ensure a
more precise positioning will probably improve the operative results in both
techniques.
97
6.6 A stentless valve with a sutureless technology (VI)
The aim of study VI was to stimulate sutureless valve function in conditions of
increased cardiac output.
Because of the increasing use of the Perceval sutureless bioprosthesis, the
assessment of its hemodynamic performance under high workload conditions
assumes a clinical importance.
Accordingly, exercise echocardiography or DSE are useful tools for the
hemodynamic evaluation of aortic valve prosthesis and may unveil a prosthetic
valve dysfunction that usually remains asymptomatic at rest [148,149].
Where valve performance at rest is concerned, we have observed similar
results compared to other recently published studies, both in terms of peak and
mean gradients or EOA [150,151] and when compared to a propensity-matched
cohort of patients undergoing TAVI [152].
Increased transvalvular gradients are general findings of aortic prostheses
investigated under stress as a result of increased heart rate and stroke volumes.
Accordingly, Khoo et al. [153] observed that stentless valves perform similarly to
mildly stenosed native aortic valves under stress, whereas stented and mechanical
prostheses resembled the performances of mild-to-moderate stenosis. Similarly,
Repossini et al. [154] described an increase in mean transvalvular gradients
during exercise in patients who had undergone AVR with the Freedom SOLO
bioprosthesis.
On the other hand, despite increased gradients, we observed a significant
increase in EOA, EOAi and DVI under stress. Similarly, the same report of
Repossini et al. [154] demonstrated an increase in EOA from 1.74±0.33 cm2 to
1.80±0.36 cm2 at exercise stress echocardiography. When these last results are
compared to the findings of our study, we observed a significantly greater
increase of EOA at DSE, reaching 2.1±0.7 cm2 at peak stress. This finding is of
particular importance, considering that the stentless Freedom SOLO and the
Perceval sutureless bioprosthesis have similar valve profile. Accodingly, Perceval
sutureless bioprosthesis can actually be considered a stentless valve with a
sutureless technology [78]. Subgroup analysis for each valve size confirmed these
results.
We could speculate that the nitinol struts, over which the pericardium is fixed,
do not interfere with valve function but rather might facilitate the opening and
closing mechanism of the leaflets according to the physiological expansion of the
aortic root during the cardiac cycle.
98
This is of particular interest, especially in those patients with small aortic
annuli, who are at greater risk for PPM. It is noteworthy that EOAi under stress
increased over 0.65cm2/m2, generally considered diagnostic for severe PPM [22].
Accordingly, Villa et al. have recently demonstrated the satisfactory performance
of the S size Perceval valve, either at discharge or early follow-up [155].
The small sample size is certainly one major limitation of Study V. However,
the single-center design of the study guarantees uniformity of the surgical
technique and of echocardiographic evaluations.
One of the major strengths of this analysis is the strict inclusion criteria used
for the enrollment of these patients. In particular, the exclusion of patients with
mitral valve regurgitation prevented any bias of Doppler quantifications.
Furthermore, in an attempt to better validate our hypothesis, we selected
patients with the longest follow-up available, in order to assess the performance
of this prosthesis long after surgery. Finally, each patient served as her/his own
control, thus limiting selection biases.
99
7 Conclusions
In the present study, the immediate and mid-term outcomes after AVR with the
Perceval sutureless prosthesis have been investigated.This study showed that
AVR with the Perceval valve is safe and effective, and allows a significant
reduction of aortic cross-clamping and cardiopulmonary bypass time. Its simple
technique of implantation may providemost of its benefits in minimally invasive
surgery, especially in patients at medium-high operative risk. Furthermore, great
adaptability to increased stroke volumes have been demonstrated.
The conclusions related to the specific questions are:
I The results of this multicenter retrospective study showed that the use of the
Perceval sutureless bioprosthesis is associated with excellent early
postoperative outcomes. The benefits of a short period of myocardial
ischemia seem pronounced in patients undergoing isolated AVR and in those
with high EuroSCORE II. Octogenarians and low-risk patients requiring
concomitant CABG may particularly benefit from this prosthesis. However,
further studies are needed to better assess the value of alternative procedures
such as TAVI or hybrid PCI in the high-risk subset of patients with severe AS
requiring concomitant procedures.
II AVR with the Perceval sutureless bioprosthesis implanted through a mini-
sternotomy is a safe and reproducible procedure. Aortic cross-clamping or
cardiopulmonary bypass times were similar to those observed during
procedures performedwith full sternotomy. Early postoperative outcomes and
2-year survival were similar between patients undergoing mini-sternotomy
and full sternotomy.
III AVR through a mini-sternotomy with implantation of the Perceval sutureless
bioprosthesis was a safe and reproducible procedure with 30-day mortality
and 2-year survival comparable to a full sternotomy with a stented
bioprosthesis. Mini-sternotomy sutureless AVR was associated with shorter
aortic cross-clamp and cardiopulmonary bypass times and reduced
transfusion of red blood cells, but a higher risk for postoperative permanent
pacemaker implantation compared to AVR through a full sternotomy with a
stented bioprosthesis.
IV Sutureless AVR and TAVI are both reasonable therapeutic strategies in
patients with severe symptomatic aortic valve stenosis. After matching, we
did not observe differences in 30-day and 1-year mortality as well as major
100
postoperative complications. AVR with the Perceval sutureless bioprosthesis
is associated with better device success and lower incidence of PVL as
compared to TAVI, even if this advantage is less evident in transapical TAVI.
On the other hand AVR with the Perceval sutureless bioprosthesis seems to
provide higher trans-aortic gradients, longer post-operative length of stay and
a trend towards higher pacemaker implantation rate. Due to the multiple
therapeutic options now available, every patient may now receive the most
appropriate treatment tailored according to her/his baseline and procedure-
related risks.
V AVR with the Perceval sutureless bioprosthesis is associated with excellent
operative survival and a low incidence of postoperative PVL. This study
suggests that the use of sutureless prostheses can improve the results of
surgery in patients at intermediate risk.
VI AVR with the Perceval sutureless bioprosthesis provides excellent
hemodynamics at rest and under DSE. The significant increase of EOAi
under DSE suggests that the Perceval sutureless bioprosthesisis the valve of
choice for patients with small aortic annuli or when PPM is anticipated.
Furthermore, Perceval could be also the solution for those patients with
calcified aortic root, in which any attempt to enlarge the annulus may
endanger the outcome of these patients.
101
8 Future perspectives
The findings of this preliminary experience with the Perceval sutureless
bioprosthesis indicate that this valve could be considered a valid alternative to
conventional aortic valve bioprostheses, particularly in patients with unfavorable
anatomic conditions. Based on these results, a prospective randomized study, the
Perceval Sutureless Implant vs Standard Aortic Valve Replacement (PERSIST-
AVR) Trial (ClinicalTrials.gov NCT02673697), have been planned in order to
compare the efficacy and durability of this sutureless bioprosthesis with
conventional, stented bioprostheses. Similarly, we are planning a prospective,
multicenter registry in order to further compare the Perceval sutureless
bioprosthesis with TAVI.
102
103
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139. van Boxtel AG, Houthuizen P, Hamad MA, Sjatskig J, Tan E, Prinzen FW & van Straten AH (2014) Postoperative conduction disorders after implantation of the self-expandable sutureless Perceval S bioprosthesis. J Heart Valve Dis 23: 319–324.
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Original publications
I Rubino AS, Santarpino G, De Praetere H, Kasama K, Dalén M, Sartipy U, Lahtinen J, Heikkinen J, Deste W, Pollari F, Svenarud P, Meuris B, Fischlein T, Mignosa C, Biancari F (2014) Early and intermediate outcome after aortic valve replacement with a sutureless bioprosthesis: Results of a multicenter study. J Thorac Cardiovasc Surg 148: 865–871.
II Dalén M, Biancari F, Rubino AS, Santarpino G, De Praetere H, Kasama K, Juvonen T, Deste W, Pollari F, Meuris B, Fischlein T, Mignosa C, Gatti G, Pappalardo A, Sartipy U, Svenarud P (2015) Mini-sternotomy versus full sternotomy aortic valve replacement with a sutureless bioprosthesis: a multicenter study. Ann Thorac Surg 99: 524–530.
III Dalén M, Biancari F, Rubino AS, Santarpino G, Glaser N, De Praetere H, Kasama K, Juvonen T, Deste W, Pollari F, Meuris B, Fischlein T, Mignosa C, Gatti G, Pappalardo A, Svenarud P, Sartipy U (2016) Aortic valve replacement through full sternotomy with a stented bioprosthesis versus minimally invasive sternotomy with a sutureless bioprosthesis. Eur J Cardiothorac Surg 49: 220–227.
IV D'Onofrio A, Salizzoni S, Rubino AS, Besola L, Filippini C, Alfieri O, Colombo A, Agrifoglio M, Fischlein T, Rapetto F, Tarantini G, Dalèn M, Gabbieri D, Meuris B, Savini C, Gatti G, Aiello ML, Biancari F, Livi U, Stefàno PL, Cassese M, Borrello B, Rinaldi M, Mignosa C, Gerosa G; Italian Transcatheter Balloon-Expandable Registry and the Sutureless Aortic Valve Implantation Research Groups (In press) The rise of new technologies for aortic valve stenosis: A comparison of sutureless and transcatheter aortic valve implantation. J Thorac Cardiovasc Surg.
V Biancari F, Barbanti M, Santarpino G, Deste W, Tamburino C, Gulino S, Immè S, Di Simone E, Todaro D, Pollari F, Fischlein T, Kasama K, Meuris B, Dalén M, Sartipy U, Svenarud P, Lahtinen J, Heikkinen J, Juvonen T, Gatti G, Pappalardo A, Mignosa C, Rubino AS (2016) Immediate outcome after sutureless versus transcatheter aortic valve eplacement. Heart Vessels 31: 427–433.
VI Rubino AS, Biancari F, Caruso V, Lavanco V, Privitera F, Rinaldi I Sanfilippo M, Millan G, D’Urso LV, Castorina S, Mignosa C (2016) Hemodynamic assessment of the Perceval sutureless valve by dobutamine stress echocardiography (Manuscript)
Reprinted with permission from Elsevier (I, II, IV, VI), Oxford University Press
(III), Springer International Publishing AG (V).
Original publications are not included in the electronic version of the dissertation.
118
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ubino
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Antonino S. Rubino
EFFICACY OF THE PERCEVAL SUTURELESS AORTIC VALVE BIOPROSTHESIS IN THE TREATMENT OF AORTIC VALVE STENOSIS
UNIVERSITY OF OULU GRADUATE SCHOOL;UNIVERSITY OF OULU,FACULTY OF MEDICINE;MEDICAL RESEARCH CENTER OULU;OULU UNIVERSITY HOSPITAL