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\begin{document}

\title{Sutureless bioprosthesis for aortic valve replacement: surgical and
clinical outcomes}



\author[1]{Ricardo Ferreira}%
\author[2]{Nuno Rua}%
\author[1]{André Sena}%
\author[1]{Tiago Velho}%
\author[1]{João Goncalves}%
\author[1]{Nádia Junqueira}%
\author[1]{Ana G. Almeida}%
\author[1]{Angelo Nobre}%
\author[1]{Fausto Pinto}%
\affil[1]{Centro Hospitalar Universitario Lisboa Norte EPE}%
\affil[2]{Universidade da Beira Interior Faculdade de Ciencias da Saude}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
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\endgroup





\selectlanguage{english}
\begin{abstract}
Aortic valve stenosis is the most common adult valve disease in
industrialized countries. The ageing population and the increase in
comorbidities urge the development of safer alternatives to the current
surgical treatment. Sutureless bioprosthesis have shown promising
results, especially in complex procedures and in patients requiring
concomitant surgeries. \textbf{Objectives:} Assess the clinical and
hemodynamic performance, safety, and durability of the Perceval
\selectlanguage{ngerman}\textsuperscript{®} prosthetic valve. \textbf{Methods:} This single
center retrospective longitudinal cohort study collected data of all
adult patients with aortic valve disease who underwent aortic valve
replacement with a Perceval \textsuperscript{®} prosthetic valve between
February 2015 and October 2020. Of the 196 patients included (mean age
77.20±5.08 years; 45.4\% female; mean EuroSCORE II 2.91±2.20\%), the
majority had aortic stenosis. \textbf{Results:} Overall mean cross-clamp
and cardiopulmonary bypass times were 33.31±14.09 and 45.55±19.04
minutes, respectively. Mean ICU and hospital stay were 3.32±3.24 and
7.70±5.82 days, respectively. Procedural success was 98,99\%, as two
explants occurred. 4 valves were reimplanted due to intra-operative
misplacement. Mean transvalvular gradients were 7.82±3.62 mmHg.
Pacemaker implantation occurred in 12.8\% of patients, new-onset atrial
fibrillation in 21.9\% and renal replacement support was necessary in
3.1\%. Early mortality was 2.0\%.~ We report no structural valve
deterioration, strokes or endocarditis and one successfully treated
valve thrombosis. \textbf{Conclusions:} Our study confirms the excellent
clinical and hemodynamic performance and safety of a truly sutureless
aortic valve, up to 5-year follow-up. These results were consistent in
isolated and concomitant interventions, solidifying this device as a
viable option for treatment of isolated aortic valve disease.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Sutureless bioprosthesis for aortic valve replacement: surgical
and clinical outcomes}

Ricardo Ferreira\textsuperscript{1,5}, Nuno Rua \textsuperscript{2},
Andr\selectlanguage{ngerman}é Sena \textsuperscript{1}, Tiago R. Velho\textsuperscript{1,3},
João Gonçalves\textsuperscript{1}, Nádia Junqueira\textsuperscript{1},
Ana G. Almeida\textsuperscript{4,5}, Ângelo Nobre\textsuperscript{1,5},
Fausto Pinto\textsuperscript{4,5}

\begin{enumerate}
\tightlist
\item
  Department of Cardiothoracic Surgery, Hospital de Santa Maria, Centro
  Hospitalar Lisboa Norte, Lisbon, Portugal
\item
  Faculdade de Ciências Médicas da Universidade da Beira Interior,
  Covilhã, Portugal
\item
  Innate Immunity and Inflammation Laboratory, Instituto Gulbenkian de
  Ciência, Oeiras, Portugal
\item
  Department of Cardiology, Hospital de Santa Maria, Centro Hospitalar
  Lisboa Norte, Lisbon, Portugal
\item
  Centro Cardiovascular da Universidade de Lisboa, Faculdade de
  Medicina, Universidade de Lisboa, Lisbon, Portugal
\end{enumerate}

\textbf{Abstract}

Aortic valve stenosis is the most common adult valve disease in
industrialized countries. The ageing population and the increase in
comorbidities urge the development of safer alternatives to the current
surgical treatment. Sutureless bioprosthesis have shown promising
results, especially in complex procedures and in patients requiring
concomitant surgeries.

\textbf{Objectives:} Assess the clinical and hemodynamic performance,
safety, and durability of the Perceval \textsuperscript{®} prosthetic
valve.

\textbf{Methods:} This single center retrospective longitudinal cohort
study collected data of all adult patients with aortic valve disease who
underwent aortic valve replacement with a Perceval
\textsuperscript{®}prosthetic valve between February 2015 and October
2020. Of the 196 patients included (mean age 77.20±5.08 years; 45.4\%
female; mean EuroSCORE II 2.91±2.20\%), the majority had aortic
stenosis.

\textbf{Results:} Overall mean cross-clamp and cardiopulmonary bypass
times were 33.31±14.09 and 45.55±19.04 minutes, respectively. Mean ICU
and hospital stay were 3.32±3.24 and 7.70±5.82 days, respectively.
Procedural success was 98,99\%, as two explants occurred. 4 valves were
reimplanted due to intra-operative misplacement. Mean transvalvular
gradients were 7.82±3.62 mmHg. Pacemaker implantation occurred in 12.8\%
of patients, new-onset atrial fibrillation in 21.9\% and renal
replacement support was necessary in 3.1\%. Early mortality was 2.0\%.~
We report no structural valve deterioration, strokes or endocarditis and
one successfully treated valve thrombosis.

\textbf{Conclusions:} Our study confirms the excellent clinical and
hemodynamic performance and safety of a truly sutureless aortic valve,
up to 5-year follow-up. These results were consistent in isolated and
concomitant interventions, solidifying this device as a viable option
for treatment of isolated aortic valve disease.

\textbf{Keywords}

Sutureless bioprosthesis; Aortic valve replacement; Perceval valve;
Aortic valve stenosis; Aortic valve disease.

\textbf{Introduction}

Aortic valve stenosis is the most frequent type of adult valvular heart
disease in industrialized countries (1). Its prevalence increases with
age with up to 9.8\% in the 80--89 year cohort (2) (3).

Conventional aortic valve replacement (AVR) through median sternotomy is
the established gold-standard for the treatment of severe and/or
symptomatic disease in patients with low-surgical risk(4). However, the
continuous increase in patients age (5) and comorbidities, the growing
percentage of patients who need concomitant surgical procedures,
combined to the fact that the duration of aortic cross-clamping and
cardiopulmonary bypass (CPB) are independent predictors of survival (6),
(7), have created the need for interventions that minimize operative
times and reduce surgical risk.

Sutureless bioprosthesis has emerged as a viable alternative combining
the best of both worlds. By avoiding sutures, it allows reduced aortic
cross-clamping, CPB and global surgical times, as well as the
possibility of complete excision of the native aortic valve and annular
decalcification, helping prevent paravalvular leaks, which is
particularly useful in patients with severe aortic stenosis and an
intermediate to high operative risk (8,9). Sutureless bioprostheses are
especially beneficial in 1) patients who are more sensitive to ischemia;
2) in technically difficult procedures (such as small and/or highly
calcified aortic roots, reoperations and in patients who require
concomitant procedures)~(10); 3) in patients with a high risk of
patient-prosthesis mismatch (PPM); and 4) in patients who require faster
recovery. Furthermore, by avoiding stitching through the annulus and
suture knotting, the risk of tearing the aortic annulus and wall or
embolizing foreign material is reduced (11). However, these advantages
must be weighed against the apparent increased risk of PPI (Permanent
Pacemaker Implantation) when compared to conventional AVR (12).

The Perceval\textsuperscript{®} valve (Sorin Group, Saluggia, Italy) is
currently the only truly sutureless valve available, with extensive
research supporting its excellent hemodynamic performance, safety, and
versatility of use. However, several questions remain unanswered, namely
long-term survival and valve durability, risk of endocarditis, the
impact of the apparent increased need for postoperative PPI and safety
of concomitant valvular procedures (13).

Our study aims to analyze the clinical and hemodynamic performance,
safety and durability of the Perceval valves implanted in patients with
aortic valve disease, both in isolated AVR as well as in patients who
underwent concomitant procedures, over a period of 5 years in a tertiary
single European center.

\section*{Materials and Methods}

{\label{materials-and-methods}}

\subsection*{Study design}

{\label{study-design}}

In this retrospective longitudinal cohort study, data of all adult
patients with aortic valve disease who underwent AVR with a
Perceval\textsuperscript{®} prosthetic valve between February 2015 and
October 2020 in Hospital de Santa Maria (Lisbon, Portugal) was
retrospectively collected from an available hospital database. Approval
of the study and access to the data was granted by the ethical committee
of the hospital involved (Comissão Ética Centro Hospitalar Lisboa Norte,
identification number: 510/18).

\subsection*{Patients}

{\label{patients}}

Data collected included demographics and preoperative characteristics,
such as comorbidities, EuroSCORE II, presence of atrial fibrillation or
pacemaker, left ventricular (LV) function and history of previous
cardiac surgery. We also collected intraoperative data, such as the
aortic cross-clamping and CPB times, size of the valves implanted and
transvalvular gradients, as well as in-hospital stay and postoperative
complications.

Endpoints were the clinical and hemodynamic performance, safety and
durability of the Perceval valve in AVR, evaluated through the following
criteria: mortality and overall long-term survival, structural valve
deterioration, operatory times (aortic clamping and CPB times), mean ICU
and total hospital stay, postoperative complications - including PPI and
infection rates (respiratory, urinary and/or bacteremia of unknown
origin), endocarditis, stroke, early mortality (defined as in-hospital
or up to 30 days after surgery), abnormal bleeding (defined as
\textgreater{} 2ml/kg/h in first 2-3 hours, \textgreater{} 1ml/kg/h in
the next 3 hours and/or \textgreater{} 0.5ml/kg/h in 12 hours),
new-onset atrial fibrillation (paroxysmal, persistent or permanent),
significant renal dysfunction (14) and need for intra-aortic balloon
pump, surgical exploration for bleeding, renal replacement support
(performed through continuous veno-venous hemodiafiltration) or
aminergic support \textgreater{}24h (performed with at least one of the
following: epinephrine, norepinephrine, dobutamine) - and postoperative
echocardiographic findings.

\subsection*{\texorpdfstring{The
Perceval\textsuperscript{®}valve}{The Perceval®valve}}

{\label{the-perceval-valve}}

The Perceval \textsuperscript{®} prosthetic valve (Sorin Group,
Saluggia, Italy) consists in 3 bovine pericardial cusps mounted on a
self-expanding nitinol stent comprising~two rings, allowing for
stabilization simultaneously at the aortic annulus and at the
sinotubular junction (STJ), and nine vertical struts covered by a thin
coating of Carbofilm\selectlanguage{english}, to improve biocompatibility. The stent holds the
valve in place without any permanent suture, by exerting radial force on
the patient's aortic annulus and aortic root. It is also flexible,
allowing it to adapt to the anatomy of the aorta and its movements, thus
relieving the stress on the leaflets. The valve is folded up by
collapsing the inflow and outflow rings with an atraumatic compression
device, allowing the pericardial leaflets not to be crimped and remain
mobile, ensuring they are not damaged (15) - in contrast to the
necessary crimping of the TAVI, in which the leaflet's collagen fibers
are damaged (10). The Perceval \textsuperscript{(r)} valve is currently
available in four sizes: S, to be implanted in annular sizes from 19 to
21 mm, M from 22 to 23 mm, L from 24 to 25 mm and XL for patients with
annular sizes of 27 mm (6).

Although the concept of sutureless bioprosthesis exists for over 40
years (16), the first reports evaluating implantation feasibility and
valve safety in humans were only released in 2007. It was CE approved in
2011 and FDA approved in 2016 (17).

\subsection*{Surgical technique}

{\label{surgical-technique}}

Indications for AVR were in agreement with the ESC/EACTS Guidelines for
the management of valvular heart disease at the time of the
interventions (18). The surgical approach was either standard median
sternotomy or upper J ministernotomy. All patients were operated on or
supervised by an experienced surgeon in this procedure. Anaesthetic and
surgical techniques were standardized. A high transverse aortotomy close
to the epiaortic fat pad was performed, leaving a free edge for closure
after implantation of the device. The native calcified aortic valve was
excised, and the aortic annulus completely decalcified. Sizing of the
annulus was done using dedicated sizers.

Concomitant procedures were performed in line with current department
practices and always with the goal of minimizing aortic cross-clamping
and CPB times. For instance, aortic graft anastomosis, when needed, was
performed prior to cannulation using tangential aortic cross-clamping.

After aortotomy closure in the usual fashion, thorough de-airing with
CO2, release of the aortic cross-clamp and weaning from CPB were
performed. Valve function was evaluated by intraoperative
transesophageal echocardiography in all patients. Following the
procedure, patients were transferred to the ICU and managed accordingly.
Antiplatelet therapy was instituted. (19).

\subsection*{Statistical analysis}

{\label{statistical-analysis}}

Statistical analysis was performed using IBM SPSS Statistics v27.1 (New
York, United States of America). Categorical variables are reported as
absolute and relative frequencies. For continuous data, means, median
and standard deviations were calculated. Cumulative survival and freedom
from events were estimated using the Kaplan--Meier method, with 95\%
confidence intervals.

\textbf{Results}

\subsubsection*{Preoperative
characteristics}

{\label{preoperative-characteristics}}

Between February 2015 and October 2020, 198 patients were submitted to
AVR with a Perceval \textsuperscript{(r)} prosthetic valve in Hospital de
Santa Maria (Lisbon, Portugal). 2 patients were excluded due to valvular
explantation, resulting in a total of 196 patients analyzed. Aortic
stenosis was the main surgery indication (96.4\%), followed by aortic
regurgitation (1.53\%), native valve endocarditis (1.02\%), prosthetic
valve endocarditis (0.51\%) and mechanic valve dysfunction (0.51\%).

Preoperative baseline characteristics of the cohort are shown in table
1. The mean overall age was 77.20+-5.08 and 45.4\% of patients were
female. EuroSCORE II predicted an in-hospital mortality risk of 2.91 +-
2.20\%. The most prevalent preoperative risk factors were impaired renal
function (85.2\%), arterial hypertension (88.3\%), overweight or obesity
(75.8\%) and dyslipidemia (71.9\%). Coronary disease was present in
34.7\% of the cohort, atrial fibrillation in 17.9\% and 8.7\% had a
history of stroke or transient ischemic attack. Most patients (69.4\%)
had preserved left ventricular function, defined as an ejection fraction
higher than 55\%.

Table 1 - Preoperative baseline characteristics and risk factors (mean +-
Standard Deviation)\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Patients\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\% (\selectlanguage{ngerman}± SD)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\textbf{Demographics}\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Sex (female)\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
45.4\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Age (in years)\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
77.20\selectlanguage{ngerman}±5.08\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
EuroSCORE II\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
2.91\selectlanguage{ngerman}±2.20\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Preserved LV function (LVEF \textgreater{}55\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
69.4\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\textbf{Risk Factors}\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Chronic Kidney Disease (CKD)\textsuperscript{1}\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
85.2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Arterial Hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
88.3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Overweight/obesity\textsuperscript{2}\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
75.8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Dyslipidemia\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
71.9\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Diabetes Mellitus (DM)\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
41.8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
DM Insulin treated\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
2.6\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Coronary Artery disease\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
34.7\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Atrial fibrillation/flutter\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
17.9\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Smoking history\textsuperscript{3}\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
18.9\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Chronic Respiratory disease\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
14.3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Peripheral arterial disease\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
4,6\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Previous stroke or transient ischemic attack\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
8,7\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Preoperative Permanent Pacemaker\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
3.1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Previous cardiac surgery\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
2.0\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{1} Impaired renal function was defined as glomerular
filtration rate \textless{}85\%

\textsuperscript{2} Overweight/obesity was defined as a body mass index
\textgreater{}25.

\textsuperscript{3} Former or active.

\subsubsection*{Intraoperative outcomes}

{\label{intraoperative-outcomes}}

Intraoperative outcomes of the cohort are shown in table 2. Overall mean
total surgery time was 131.67\selectlanguage{ngerman}±56.71 minutes, with mean aortic
cross-clamping and CPB times of 33.31±14.09 minutes and 45.55±19.04
minutes, respectively. Of all surgeries, 15 (7.65\%) were minimally
invasive, via upper J mini-sternotomy.

The M size of Perceval \textsuperscript{®} valve was the most frequently
implanted prothesis, accounting for 69 patients of the entire cohort
(35.6\%), followed by the size L in 64 patients (33.0\%), XL in 35
(17.0\%) and the size S in 28 (14.4\%).

Isolated AVR was performed in 122 (62.24\%) patients. Concomitant single
CABG surgery was performed in 22 (11.22\%) patients, double CABG surgery
in 23 (11.73\%) and triple CABG surgery in 4 (2.04\%). Other concomitant
procedures included mitral and/or tricuspid valvular repair/replacements
in 12 patients (6.12\%), Morrow procedure in 10 (5.10\%), supracoronary
ascending aorta replacement in 2 (1.02\%) and Dor procedure in 1
(0.51\%) patient. 2 patients (1.02\%) had already undergone previous
cardiac surgery.

The Perceval \textsuperscript{®} valve was successfully implanted in 196
patients (98.98\%), whereas in 2 cases (2/198 = 1.01\%), conversion to
conventional bioprosthesis (Edwards Perimount Magna
Ease\textsuperscript{®}) was required after valve explantation due to
severe displacement. In 4 cases (2/196 = 2.04\%) reimplantation was
necessary to readjust the valve, due to misplacement/paravalvular leaks.

Table 2 - Intraoperative outcomes (mean ± SD)\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Patients\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Patients\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
n = 196\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\%\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Operatory data}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Operatory data}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Total surgery (minutes)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Total surgery (minutes)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
131.67\selectlanguage{ngerman}±56.71\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Cardiopulmonary bypass (minutes)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Cardiopulmonary bypass (minutes)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
45.55\selectlanguage{ngerman}±19.04\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Aorta cross-clamping (minutes)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Aorta cross-clamping (minutes)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
33.31\selectlanguage{ngerman}±14.09\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Valve size\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Valve size\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
S (\emph{n})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
S (\emph{n})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
28\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14.4\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
M (\emph{n})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
M (\emph{n})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
69\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35.6\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
L (\emph{n})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
L (\emph{n})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
64\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
33.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
XL (\emph{n})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
XL (\emph{n})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
17.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Intra-operative valve complications}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Intra-operative valve complications}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Reimplantation\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Reimplantation\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Significant paravalvular leaks\textsuperscript{1}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Significant paravalvular leaks\textsuperscript{1}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Operation Details}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Operation Details}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Isolated aortic valve replacement\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Isolated aortic valve replacement\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
122\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
62.24\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
+CABG x1\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
+CABG x1\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
22\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
11.22\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
+CABG x2\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
+CABG x2\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
23\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
11.73\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+CABG x3\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+CABG x3\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.04\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+Mitral/Tricuspid Repair/Replacement\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.12\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+Morrow Miectomy\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+Morrow Miectomy\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
10\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5.10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+Ascending aorta replacement\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+Ascending aorta replacement\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.02\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+Dor procedure\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
+Dor procedure\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.51\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Previous cardiac surgery\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Previous cardiac surgery\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.02\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Minimally Invasive Approach\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Minimally Invasive Approach\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.65\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Mean transvalvular gradients (mmHg)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Mean transvalvular gradients (mmHg)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.82\selectlanguage{ngerman}±3.62\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\subsubsection*{Postoperative outcomes}

{\label{postoperative-outcomes}}

Postoperative results are shown in table 3. The average ICU stay was
3.32\selectlanguage{ngerman}±3.24 days and the average total hospital stay 7.70±5.82 days. Mean
transvalvular gradients were 7.82±3.62 mmHg. 4 patients (2.04\%) died,
one due to refractory cardiogenic shock, two due to septic shock and
multiorgan failure following urgent surgery for native valve
endocarditis and one after neurologic complications related to an
underlying type A aortic dissection.

The most common immediate postoperative complications over the entire
cohort were the need for aminergic support for over 24 hours (45.1\%),
new-onset atrial fibrillation (21.9\%), PPI (12.8\%) and significant
acute kidney injury (AKI) (10.5\%). Less prevalent postoperative
complications included infections (10.2\%), abnormal bleeding (9.2\%),
renal replacement support (3.1\%), early mortality (2.0\%), intra-aortic
balloon pump implantation (2.0\%) and the need for surgical exploration
for bleeding (1.0\%).

During follow-up, no structural valve deterioration, strokes, or
endocarditis were reported. One patient developed valve thrombosis
(0.5\%), which was successfully treated with oral anticoagulants. Figure
1 shows the overall Kaplan-Meier cumulative survival curve throughout 5
years. The survival rate at the end of 1 year was 94\%, at 3 years 86\%
and 5 years 71\%.

Table 3 -- Postoperative outcomes (mean ± SD)\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Patients\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\%\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\textbf{In-hospital stay}\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
ICU stay (days)\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
3.32\selectlanguage{ngerman}±3.24\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Hospital stay (days)\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
7.70\selectlanguage{ngerman}±5.82\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\textbf{Post-operative complications}\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Aminergic support \textgreater{}24h\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
45.1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
New-onset Atrial fibrillation\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
21.9\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
PPI\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
12.8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Significant AKI\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
10.5\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Infection\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
10.2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Abnormal bleeding\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
9.2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Renal replacement support\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
3.1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Early mortality\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
2.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Intra-aortic balloon pump\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
2.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Surgical exploration for bleeding\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
1.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Valve thrombosis\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
0.5\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Stroke\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
0.0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Endocarditis\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
0.0\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

ICU: intensive care unit

PPI: Permanent pacemaker implantation

AKI: acute kidney injury\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image10/image10}

\end{center}
\end{figure}

Figure 1 -- Follow-up overall mortality (Kaplan--Meier survival curve)

Discussion

The Perceval \selectlanguage{ngerman}\textsuperscript{®} prosthetic valve (Sorin Group,
Saluggia, Italy) has been increasingly used in European cardiac surgery
centers for treatment of aortic valve disease since its first reports in
2007. As a truly sutureless bioprosthesis with proven excellent
hemodynamic outcomes, safety and marked reduction in aortic
cross-clamping and CPB times, it has been shown to reduced postoperative
morbidity and mortality as well as cost reduction of up to 25\% when
compared to conventional biological heart valves (8,20), especially when
treating older patients and in those with comorbidities. However,
several questions are yet unanswered, especially regarding long-term
durability, endocarditis risk, and the need for postoperative PPI.

In our retrospective study, we sought out to assess the clinical and
hemodynamic performance, safety, and durability of the
Perceval\textsuperscript{®} valve for isolated AVR and in concomitant
procedures.

Our cohort is composed essentially by elderly patients, with an average
overall age of over 77 years and a small standard deviation of
approximately 5 years. Additionally, most patients had one or more
preoperative risk factors and/or comorbidity, with an average
in-hospital mortality risk measured by an EuroSCORE II of almost 3\%,
despite the majority having preserved LV function.

The overall total surgical time, aorta cross-clamping and CPB times took
into consideration the surgeries where reimplantation of the valve was
necessary. The times obtained represent a significant reduction in
comparison to the mean aorta cross-clamping and CPB times of 78 and 106
min reported in conventional AVR, according to the Society of Thoracic
Surgeons database. This major reduction of over 50\% in both times could
translate into improved clinical results, especially in patients with
comorbidities such as diabetes mellitus (7) or in a medium-high surgical
risk profile, as aortic clamping and CPB times are considered
independent predictors of morbidity and mortality in heart surgery (10).

The Perceval \textsuperscript{®} valve was successfully implanted in
98.99\% as in 2 cases (2/198 = 1.01\%) conversion to conventional
bioprosthesis was required due to valve migration. One way of possibly
reducing the likelihood of these events is by strictly obliging the
manufacturer's preoperative echo-doppler aortic root evaluation
recommendations (a patient is suitable if the ratio between the diameter
of the STJ and the annular diameter is \selectlanguage{english}[?] 1,3) (21).

In 4 cases (2.04\%) reimplantation was necessary to readjust the valve,
due to minor misplacement and/or paravalvular leaks found in the
intraoperative transesophageal echocardiography, which is paramount to
assure correct placement and function. Reimplantation through the
``x-movement'' technique, allowed an \emph{``en bloc''} bioprosthesis
excision, simple re-folding and easy reimplantation of the valve without
damage to the leaflets or the bioprosthesis structure. (22). Reasons for
these misplacements are still unclear but in one of the cases, migration
followed cardiac manual manipulation due to additional manual de-airing.
(23).

In our study, we report no significant paravalvular leaks, a result
below the already low 1-2\% commonly observed in trials with the
Perceval \textsuperscript{(r)} valve (6). In comparison, TAVI causes a
greater number of moderate-to-severe paravalvular leaks (7-12\%),
followed by conventional AVR (1,9\%), which at 2 years have been shown
to be independent predictors of mortality (10,24). Consequently, correct
measurement, placement and final visual confirmation of correct valve
placement could help avoid these complications.

The most common immediate postoperative complications (Table 3) were in
line with the expected for a major cardiac procedure. The relatively
high rate of postoperative aminergic support might be related to the
fluid restriction protocol used in our department. New-onset atrial
fibrillation is usually multifactorial and is the most common
dysrhythmic complication occurring after any cardiac surgery, affecting
typically between 30\% and 50\% of the patients, more than we report
(25). Although the incidence of acute kidney injury is relatively high
(10,5\%), only a reduced number of patients required renal replacement
technique (3,1\%).

The overall incidence rate for PPI of 12.8\% is within the interval
incidence described in the literature, of 3.1\% (26) to 17\% (27)
although it is above rates for conventional bioprosthesis reported of
3.0 to 11.8\% (28) and comparable to the ones reported for TAVI (29).
Current best available evidence suggests baseline conducting system
disease is the most powerful independent predictor of PPI requirement
following AVR. Other patient-related predictors are advanced age,
annular calcification, (27). Operative-related factors such as
incomplete decalcification of the aortic ring, valve oversizing, valve
and guiding sutures position, reoperations, longer perioperative CPB
time, and procedural implanting steps and sizing's learning curve effect
are also important (13). In our center, all patients were operated on or
supervised by an experienced surgeon in this procedure. That said,
standardizing the implantation technique could offer benefits in
reducing the PPI incidence.

We report one case of valvular thrombosis (0.51\%), which was
successfully treated with oral anticoagulants (Vitamin K antagonist).
Following the procedure, all patients received antiplatelet treatment
according to the standard protocol in use in our center, consisting of
acetylsalicylic acid or clopidogrel for a period of 3 to 6 months when
sinus rhythm was present.~ Antiplatelet and anticoagulation management
after sutureless valve placement is not standardized, as no specific
recommendations have been made in recent guidelines (17).

We found no structural valve deterioration, endocarditis cases or
strokes up to the 5-year follow-up, presumably because the
Perceval\textsuperscript{(r)} valve allows less manipulation of the aortic
root and annulus, zero permanent contact with foreign material such as
sutures (13) and it has been shown to present high resistance against
endocarditis in comparison with conventional prostheses. Nevertheless, 5
years of follow-up is still a short time compared to the data available
for conventional prostheses of up to 25 years (30).

The mean postoperative transvalvular gradients after surgery confirm the
excellent hemodynamic performance of the Perceval
\textsuperscript{(r)}valve, coherent with other studies (6) and
significantly lower when compared to the ones provided by conventional
prostheses (28) and TAVIs (29).

ICU and total in-hospital stay were markedly lower when compared to
reports of conventional bioprostheses (31) and similar when compared to
TAVIs (29).

Early overall mortality (in-hospital or up to 30 days after surgery) was
2.0\%, below the one predicted by the initial EuroSCORE, in line with
the 2.8\% reported for conventional prostheses and significantly lower
than with TAVIs (10,30,32,33). Of the four patients who died, none of
their deaths was caused directly from a failure in the prosthetic valve
or the procedure themselves (cardiogenic and septic shock, neurological
complications). These results show good short-term clinical outcomes
despite the risk profile and advanced age of the cohort.

Overall cumulative survival at 1, 3 and 5 years and the correspondent
Kaplan-Meier curve are the ones expected taking into consideration our
cohort's age, comorbidities, and type of interventions. It is up to par
with the mean corresponding cumulative survival of conventional AVR (34)
and better than with TAVIs up to 2 years (29), showing safety of use and
good mid-term durability, with no structural valve deterioration.

Additionally, the Perceval \textsuperscript{(r)} valve enables
standardization and simplification of MIS approaches, in a way
conventional prostheses have not yet made possible. MIS is associated
with a significant technical difficulty due to reduced visualization
that increases aortic cross-clamping and CPB time, extending the
learning curve (10).

\section*{Conclusions}

{\label{conclusions}}

All patients with indication for AVR with a biological bioprosthesis
could potentially benefit from a shorter and easily reproducible
treatment. This seems to be especially beneficial in patients more
sensitive to ischemia, technically difficult procedures, patients with a
high risk of PPM, and patients who require faster recovery.

Our study further confirms the excellent clinical and hemodynamic
performance and safety of the Perceval \textsuperscript{(r)} valve, a
truly sutureless aortic prothesis, in a moderately large cohort of
patients, even up to the 5-year follow-up. Consistent with current
literature, the Perceval \textsuperscript{(r)} valve allowed reduced
aortic cross-clamping, CPB and surgical times due to its easy and rapid
implantation technique as well as low rates of mortality, complications,
or dysfunctions early and up to 5 years, even in our cohort of mostly
older patients with comorbidities. Additionally, it has been proven to
facilitate the reproducibility and resurgence of minimally invasive
approaches, reducing additional postoperative complications.

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{\label{bibliography}}

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