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Cite this article as: Yousif A, Ali K, Anssar M, Harringer W, El-Essawi A, Brouwer R. A 20-year experience with cryopreserved allografts as the valve replacement of
choice in aortic root reconstruction for destructive endocarditis with abscess formation. Interact CardioVasc Thorac Surg 2022; doi:10.1093/icvts/ivac188.
A 20-year experience with cryopreserved allografts as the valve
replacement of choice in aortic root reconstruction for destructive
endocarditis with abscess formation
Afram Yousif
a,
*, Khaldoun Ali
a
,MarcelAnssar
a
, Wolfgang Harringer
a
, Aschraf El-Essawi
b,†
and
Rene´Brouwer
a,†
a
Department of Cardiothoracic and Vascular Surgery, Braunschweig Clinic, Braunschweig, Germany
b
Department of Cardiothoracic and Vascular Surgery, University of Go¨ttingen, Go¨ttingen, Germany
* Corresponding author. Department of Cardiothoracic and Vascular surgery, Braunschweig Clinic, Salzdahlumerstraße 90, 38126 Braunschweig, Germany.
Tel: +495315952213; e-mail: aframyo@hotmail.com (A. Yousif).
Received 8 March 2022; received in revised form 23 June 2022; accepted 29 June 2022
Abstract
OBJECTIVES: The aim of this retrospective study was to assess the early- and long-term outcomes following the use of cryopreserved
allografts in aortic valve endocarditis with peri-annular abscess formation.
METHODS: From 2001 to 2021, 110 consecutive patients with active infective endocarditis and peri-annular abscess, underwent a
cryopreserved allograft root replacement. In 100 patients (91%), the operation was performed <48 h after admission due to refractory heart
failure and or septic shock. In 95 patients (86.4%), a redo operation was performed due to a prosthetic valve endocarditis. Preoperatively,
12 patients were dialysis-dependent and 30 patients suffered from a recent stroke.
†
These authors contributed equally to this work.
ADULT CARDIAC
V
CThe Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-
nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use,
please contact journals.permissions@oup.com
Interactive CardioVascular and Thoracic Surgery 2022, 35(2), ivac188 ORIGINAL ARTICLE
https://doi.org/10.1093/icvts/ivac188 Advance Access publication 4 July 2022
RESULTS: The 30-day mortality was 18% (20 patients). Freedom from reintervention was 98.3% (standard deviation: 1.7) at 1 year and
83.3% (standard deviation: 8.5) at 10 years. Four patients required a redo operation. Three patients did develop re-endocarditis. Freedom
from re-endocarditis was 95% after 17 years of follow-up. Preoperative dialysis dependency (odds ratio: 22.75, 95% confidence interval:
4.79–108.14, P< 0.001), ejection fraction under 30% (odds ratio: 17.91, 95% confidence interval: 3.27–98.01, P< 0.001) and stroke
within 14 days prior to operation (odds ratio: 5.21, 95% confidence interval: 1.28–21.2, P= 0.021) were incremental factors associated with
the 30-day mortality.
CONCLUSIONS: In aortic root endocarditis with abscesses formation, cryopreserved allografts exhibit excellent clinical performance with
a low rate of reinfection and reintervention, which make its use as valve replacement a very desirable option. Dialysis dependency, ejection
fraction under 30% and recent stroke have the highest impact on the 30-day mortality.
Keywords: Cryopreserved allografts • Aortic valve endocarditis • Root abscess • Aortic root reconstruction • Long-term results
ABBREVIATIONS
CI confidence interval
ECLS Extracorporeal life support system
OR Odds ratio
PVE Prosthetic valve endocarditis
SD Standard deviation
INTRODUCTION
Active infective aortic root endocarditis of native or prosthetic
valves is a life-threatening condition with mortality ranging be-
tween 26% and 75% [1]. In 20% of the cases, burrowing ab-
scesses develop around the annulus with resulting destruction
of the aortic root, the aortic-mitral continuity or fistula forma-
tion into a cardiac chamber [2,3]. These life-threatening com-
plications need aggressive debridement of the abscesses and
reconstruction of the deformed aortic root with a suitable valve
replacement. After surgical treatment, the in-hospital mortality
ranges between 10% and 40% [3]. Several factors have been
identified as predictors for in-hospital mortality including hae-
modynamic deterioration due to cardiogenic or septic shock,
staphylococcal infection, prosthetic valve endocarditis (PVE)
and urgent operation [1,4,5].
Currently, the surgeon’s armamentarium for aortic root re-
construction consists of cryopreserved allografts, pericardial
tissue xenografts, biological aortic root prostheses and me-
chanical prosthetic valve conduits. Their optimal performance
is dependent upon the grafts0resistance to infection and in vivo
durability. A final discussion as to which valve replacement is su-
perior has not been resolved yet mostly due to the scarceness of
randomized studies. Some favour the conventional mechanical or
biologic valve prosthesis due to the unavailability of the cryopre-
served allograft and the complexity of the implantation technique,
whereas others favour the use of the cryopreserved allograft for its
tissue characteristics [6–9].
In the past 20 years at our institution, cryopreserved allograft
was the valve replacement of choice for reconstruction of the de-
formed aortic root due to destructive endocarditis with extensive
abscess formation. The goal of this single-centre study was first
to determine the durability of the cryopreserved allograft by
assessing the incidence of surgical reintervention and/or the re-
currence of endocarditis and second to identify incremental fac-
tors associated with the 30-day mortality after cryopreserved
allograft implantation.
PATIENTS AND METHODS
Ethics statement
The local ethical committee (Hannover Medical School—Nr
8718_BO_K_2019) approved the study and waived the need for
individual patient consent.
Study design
The study cohort comprised patients who underwent a cryopre-
served allograft replacement for reconstruction of the deformed
aortic root caused by destructive endocarditis with concomitant peri-
annular abscess formation. The data were retrospectively retrieved
from our departments’ database and included patients operated be-
tween 2001 and 2021. The diagnosis of endocarditis was determined
according to the modified Duke criteria [10] and confirmed by histo-
pathological examination and tissue cultures postoperatively.
Once a peri-annular abscess was confirmed or highly suspected
in the transoesophageal echocardiography, an allograft was ordered
via the German society for tissue transplantation bank. In the case of
PVE, the same valve size as in the previous operation was ordered,
or one size bigger, if the same size was not available (mostly 23–
25 mm). In the case of native valve endocarditis, we anticipated the
size to avoid patient-graft mismatch (again mostly 23–25 for women
and 23–27 mm for men). If the diagnosis was confirmed intraopera-
tively the allograft was used, otherwise, it was kept frozen and
returned to the tissue bank. Patients treated otherwise were not in-
cluded in our analysis. Primary outcomes included 30-day mortality
as well as long-term survival and long-term freedom from re-
endocarditis and reintervention. Reoperation was defined as any op-
eration that repairs or replaces the previously implanted allograft.
Re-endocarditis was defined as any infection involving the operated
valve according to the modified Duke criteria and histological con-
firmation of endocarditis at reoperation. Secondary outcomes in-
cluded factors associated with the 30-day mortality. The EuroSCORE
was calculated based on a set of predefined preoperative risk factors
[11]. Anti-bacterial therapy was antibiogram dependent and in com-
pliance with the guidelines. It was always continued intravenously
for 6–8 weeks following the procedure. Patients with an isolated allo-
graft implantation received Heparin in a prophylactic dose up till
discharge. Afterwards, no further anticoagulants were prescribed.
Further therapies were dependent on concomitant procedures or
comorbidities of the patients. Patients with an additional coronary
artery bypass grafting received Aspirin 100 mg once a day, patients
with an additional tricuspid valve or mitral valve reconstruction and/
2A. Yousif et al. / Interactive CardioVascular and Thoracic Surgery
or replacement or atrial fibrillation received oral anticoagulation
with phenprocoumon.
Allograft function was assessed with echocardiography in all
patients before discharge. The mean and peak transvalvular gra-
dients as well as the degree of valve incompetence were
reported. Follow-up data were obtained prospectively during
follow-up visits or by contacting cardiologists, general practi-
tioners or the patients themselves.
Surgical details
Surgery was performed after standard median sternotomy with the
use of cardiopulmonary bypass and crystalloid cardioplegia under
mild systemic hypothermia (32C). The aortic valves, native or
prosthesis were resected and the deep abscesses fully debrided.
After anti-septic irrigation, the coronary ostia were excised using the
button technique. The proximal anastomosis between the cryopre-
served allograft and left ventricle outflow tract was performed using
single interrupted 4-0 polypropylene sutures, placing them circum-
ferentially around the annulus, ensuring full-thickness bites of tissue.
In case of an aortoventricular dehiscence, closure of the septal de-
fect was achieved with the attached aortic-mitral ‘curtain’ of the cry-
opreserved allograft. The coronary ostia were re-implanted as
buttons into the cryopreserved allograft conduit. Other intra-cardiac
defects were closed with either autologous or bovine pericardium.
In case of proximal and/or total aortic arch replacement, deep hy-
pothermic circulatory arrest was applied. The operative procedure
is described more extensively in Supplementary Material, Fig. S1.
Statistical analysis
The distribution of the continuous variables was analysed with
normality plots. If they were normally distributed, the mean and
standard deviation (SD) were used, if not the median with the 25th
and 75th percentiles were used. Categorical variables are pre-
sented as total count and percentage of the group. Missing values
were excluded listwise and excluded from all analyses.
Multicollinearity among 2 or more independent variables was
ruled out by the Variance Inflation Factor and Condition index.
Overall survival was examined by the Kaplan–Meier estimate with
95% confidence interval (CI). Freedom from events (re-endocardi-
tis and reintervention) was adjusted for competing risk with mor-
tality using the Fine–Gray method. Pre- and intraoperative
variables were tested in a univariable fashion as a pre-screening
method and variables with a P< 0.25 were included in the model.
The lowest Akaike Information Criterion Value in combination
with the highest Pseudo R
2
(Nagelkerke) determined which model
fitted best for the data and the predictive strength. A forward mul-
tivariable logistic regression analysis was run to find the adjusted
odds ratio (OR) for each variable with 95% CI. Statistical analysis
was performed using SPSS version 28 (IBM142 Corp., Armonk, NY,
USA) and R-software (version 2.2–10. Copyright V
C2020 the R
Foundation for Statistical Computing) was used for data analysis.
P-values <_0.05 are considered statistically significant.
RESULTS
Preoperative demographic characteristics
One hundred and ten consecutive patients (87 males, 79.1%)
with a median age of 70 years underwent a cryopreserved
Table 1: Patient demographic and baseline characteristics
Characteristics N(%)
Number of patients 110
Age (years) median (25th to 75th percentile) 70 (60, 75)
Gender, male 87 (79%)
BMI (kg/m
2
)
<25 37
25–29.9 41
>_30 32
COPD 14 (13%)
Pulmonary hypertension 13 (13%)
PAVD 33 (30%)
CVD 57 (52%)
DMII 24 (22%)
IDDMII 9 (8%)
Rhythm disturbances 60 (55%)
AF 39 (35%)
Complete AV block 12 (11%)
PM-dependent 9 (8%)
Ejection fraction
>50% 56 (51%)
30–50% 46 (42%)
<30% 8 (7%)
NYHA class
I–II 12 (11%)
III–IV 98 (89%)
Active endocarditis and root abscess 110 (100%)
Preoperative dialysis dependent 12 (11%)
Preoperative stroke 30 (27%)
<2 weeks before surgery 16
>2 weeks before surgery 14
Previous heart surgery 95 (86%)
Isolated aortic valve replacement 42
Aortic valve replacement:
+CABG 21
+Ascending aortic replacement 12
+Ascending, arch and frozen ET 1
+CABG and ascending aortic replacement 4
+Mitral or tricuspid valve surgery 5
David procedure and ascending aortic replacement 3
+Arch replacement 1
Homograft aortic valve replacement 2
Freestyle aortic root replacement 2
CABG and ascending aortic replacement 2
AF: atrial fibrillation; BMI: body mass index; CABG: coronary artery bypass
grafting; COPD: chronic obstructive pulmonary disease; DMII: diabetes
mellitus type II; IDDMII: insulin-dependent diabetes mellitus type II; MVR:
mitral valve replacement; NYHA: New York Heart Association classification;
PAVD: peripheral arterial vessel disease; PM: pacemaker; SD: standard devi-
ation; TV: tricuspid valve.
Table 2: Isolated microorganisms
Causative microorganism N(%)
Staphylococcus aureus 21 (19)
Staphylococcus coagulase negative 5 (5)
Staphylococcus epidermidis 14 (13)
Streptococcus species 7 (6)
Enterococci 28 (25)
Miscellaneous 10 (9)
No microorganism identified 25 (23)
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3A. Yousif et al. / Interactive CardioVascular and Thoracic Surgery
allograft replacement. The majority of the patients (N= 98, 89%)
were classified as New York Heart Association Class III or IV,
while 25 (23%) of them were in septic shock. Twelve patients
(11%) were dialysis dependent at the time of admission. Thirty
patients (27%) had a recent, likely septic, stroke, 14 of them
within 2 weeks prior to surgery. In 27 patients, the diagnosis was
confirmed by a cerebral computed tomography scan and in 3
patients by a magnetic resonance imaging scan. All of these
patients had a stable neurological condition prior to surgery so
that their neurological impairment was not seen as a contraindi-
cation for surgery.
Twelve patients (11%) had a complete atrioventricular block.
An urgent (within 48 h after admission) or emergent operation
was performed in 100 patients (91%) due to congestive heart fail-
ure, septic shock, presence of large vegetations, severe aortic re-
gurgitation, fistulas or recurrent systemic embolization. Eighty-six
(78%) underwent reoperative sternotomy and 9 patients (8%)
underwent second or third reoperative sternotomy. Of these, 50
patients had a previous bio-prosthetic aortic valve replacement
and 35 patients a mechanical aortic valve replacement. Three
patients had a previous endocarditis of which 2 were operated in
another clinic. In 15 patients (14%), a native valve endocarditis
was found, of those 3 had a bicuspid valve.
The median logistic EuroSCORE of the whole group was 17.8%
(25th to 75th percentile: 9.6–35.4). The miscellaneous primary
operations are listed in Table 1. A causative microorganism was
identified in 85 (77.3%) patients (Table 2). In 25 patients (23.7%),
the blood and histopathological cultures remained sterile as
blood culture-negative endocarditis group.
Intraoperative characteristics
Twenty-seven patients underwent a concomitant coronary ar-
tery bypass grafting, in 12 of those, coronary artery bypass
grafting was needed due to severe ostial calcification and or
destruction by the abscess formation and in one case a vein
graft interposition between the coronary ostium and the allo-
graft was needed. Eight patients required a proximal aortic arch
replacement and 3 patients a total arch replacement. Other sur-
gical characteristics and intraoperative details are summarized
in Table 3.
Early mortality and morbidity. The operative 30-day mortal-
ity was 18% (20 patients). Causes of death were multi-organ fail-
ure (n= 11), low cardiac output syndrome (n= 4), intraoperative
death due to haemorrhagic shock (n= 1), cerebrovascular acci-
dent (n= 2), pulmonary haemorrhage (n= 1) and one with sud-
den cardiac death. In 7 patients, a preoperative complete
atrioventricular block persisted postoperatively, while 21 patients
developed a new atrioventricular clock postoperatively, all re-
quiring a pacemaker implantation. The other postoperative data
are listed in Table 4.
Allograft function before hospital discharge. Mean trans-
valvular gradient was 4.5 (SD: 2.2) mmHg, with a peak transvalvu-
lar gradient of 8.3 (SD: 4.1) mmHg. All patients had no or trivial
aortic valve incompetence.
Factors associated with 30-day mortality. Predictors of
30 -day mortality are presented in Table 5. Multivariable analysis
identified the following variables as statistically significant: preopera-
tive dialysis dependency (OR: 22.75, 95% CI: 4.79–108.14, P< 0.001),
ejection fraction under 30% (OR: 17.91, 95% CI: 3.27–98.01,
P< 0.001) and stroke within 14 days prior to operation (OR: 5.21,
95% CI: 1.28–21.2, P= 0.021; Table 6).
Follow-up. The mean follow-up time was 4.0 years (range
0– 1 7 . 1 years) with a follow-up index of 0.48 (SD: 0.39). During the
Table 3: Intraoperative data
Type of operation N(%)
Ascending aortic replacement 110 (100)
CPB time, min, median (25th to 75th percentile) 254 (241, 254)
Cross-clamp time, min, median (25th to 75th percentile) 174 (165, 174)
Aortic arch replacement 11 (10)
Proximal 8 (7)
Total 3 (3)
Coronary artery bypass graft 27 (25)
Mitral valve surgery 16 (15)
Repair 5 (5)
Replacement 11 (10)
Tricuspid valve surgery 7 (6)
Repair 4 (4)
Replacement 3 (2)
Carotid endarterectomy 2 (2)
Atrial repair 6 (6)
ASD closure 1 (1)
VSD closure 1 (1)
PM removal 9 (8)
Need for IABP 3 (3)
Need for ECLS 5 (5)
ASD: atrial septal defect; CPB: cardiopulmonary bypass; ECLS: extra corpo-
real life support system; IABP: intra-aortic balloon pump; PM: pacemaker;
VSD: ventricular septal defect.
Table 4: Postoperative data
Characteristics N(%)
30-day mortality 20 (18%)
New-onset renal failure 17 (15%)
LCOS 20 (18%)
Need for IABP 3 (2%)
Postoperative bleeding requiring rethoracotomy 24 (22%)
Requiring CPB 4 (3%)
Respiratory failure requiring reintubation 13 (12%)
Neurologic events
Stroke 3 (2%)
Intracranial haemorrhage 1 (1%)
Delirium 29 (26%)
Sternal infection 1 (1%)
Sepsis 11 (10%)
Postoperative rhythm disturbances
Atrial fibrillation 8 (11%)
Complete AV-block requiring PM implantation 28 (26%)
Ventricular fibrillation 2 (2%)
Blood product transfusion (units) Mean (SD)
PRBCs 11.7 (9)
FFP 12.7 (10)
PLT 2.1 (2)
ICU-stay, days 10 (15)
Hospital stay, days 16 (12)
CPB: cardiopulmonary bypass; FFP: fresh frozen plasma; LCOS: low cardiac
output syndrome; PLT: platelet concentrates; PRBC: packed red blood cells.
4A. Yousif et al. / Interactive CardioVascular and Thoracic Surgery
follow-up period, another 36 patients died from various
causes: 6 patients due to heart failure; 5 patients due to sepsis
and multi-organ failure, of which none due to re-endocarditis,
3 patients due to renal failure; 2 patients due to respiratory
failure; 2 patients due to a cerebrovascular accident; 2 patients
due to bleeding complications and 7 patients due to natural
non-cardiac-related death (see Supplementary Material). In 9
patients, cause of death was unknown. One patient was lost to
follow-up. The long-term survival was 67.6% (SD: 0.4) at
1 year, 51.2% (SD: 0.5) at 5 years, 31.4% (SD: 0.6) at 1 0 years
and 19.4% (SD: 0.6) at 15 years (Fig. 1).
Four patients required a redo operation, 2 due to recurrent
endocarditis after 1.4 and 6 years of follow-up and 2 due to
structural graft degeneration after 2.6 and 8.1 years of follow-up,
respectively. Freedom from reintervention was 98.3% (SD ± 1.7)
at 1 year, 90.8% (SD ± 5.7) at 5 years and 83.3% (SD ± 8.5) at
10 years (Fig. 2A).
Three patients did develop re-endocarditis (2.7%). Two of
these patients needed a reoperation, one patient was treated
medically. Overall absence of recurrent endocarditis was 95% up
to 17 years of follow-up (Fig. 2B).
DISCUSSION
In infective endocarditis, the choice of valve and/or conduit is
guided by factors such as the presence of PVE, the integrity of
the aortic root, need for anticoagulation, the availability of
cryopreserved allografts and surgical experience [1,7]. In the
case of an intact aortic root, the preference for mechanical or
bio-prosthetic valves is understandable, but in cases of invasive
infective endocarditits (IE) with concomitant peri-annular ab-
scesses, the role of aggressive debridement and root replace-
ment rather than simple aortic valve replacement is crucial. In
our series, all patients had extensive aortic root abscess and 86%
had PVE, some of those underwent multiple reoperative sternot-
omies. At presence, there are no prospective randomized studies
to support decision-making in this subpopulation. However, in a
systematic review and meta-analysis, Yanagawa et al. [12] exam-
ined 2232 patients in 18 observational studies to compare the
outcomes between allograft and conventional prosthesis for na-
tive valve endocarditis (NVE) and PVE. The median number of
patients with PVE in these studies was 30%. No differences were
found in early mortality or stroke nor in long-term outcomes of
all-cause mortality, recurrent endocarditis and reoperation be-
tween allograft versus all conventional prosthesis. However,
there were significantly more reoperations with allograft as com-
pared to the mechanical prosthetic valves. Furthermore, there
was a higher incidence of peri-annular abscess, root replace-
ment and reoperation for PVE in the allograft cohort, with signif-
icantly longer cardiopulmonary bypass and cross-clamp times.
This could implicate a greater disease burden in this cohort.
Given that there was no statistical difference in operative mortal-
ity between these groups, one could presume that allografts may
have better outcomes in these high-risk patients. Like others, we
contend that the use of allografts in this subset of patients may
offer distinct surgical technical advantages for several reasons
[6–9,13]. First, the complex reconstruction after aggressive de-
bridement of the root can be better accommodated by the
allografts due to its tissue components such as the aortomitral
Figure 1: The Kaplan–Meier survival curve after allograft implantation for na-
tive and prosthetic valve endocarditis.
Table 5: Univariable logistic regression analysis for 30-day
mortality
Characteristics Odds ratio (95% CI) P-value
Gender 1.6 (0.43–6.0) 0.48
Prior cardiac surgery 3.5 (0.43–28.3) 0.24
CPB time 0.1 (0.99–1.0) 0.87
Aortic cross-clamp time 1.0 (0.99–1.0) 0.65
COPD 3.0 (0.88–10.2) 0.08
Pulmonary hypertension 2.3 (0.62–8.2) 0.22
Extracardiac arteriopathy 2.9 (1.01–7.89) 0.04
Coronary artery disease 0.95 (0.35–2.4) 0.86
Rhythm disorders 1.39 (0.89–2.16) 0.15
DMII 3.08 (1.08–8.77) 0.04
Ejection fraction under 30% 5.38 (1.22–23.73) 0.03
NYHA III/IV 2.70 (1.11–6.55) 0.03
Preoperative dialysis 23.73 (5.57–101.1) <0.001
Prior stroke 0.23 (0.05–1.08) 0.06
Stroke within 14 days prior to operation 4.85 (1.54–15.28) 0.007
Concomitant aortic arch surgery 3.50 (0.89–13.82) 0.07
BCNIE 0.32 (0.07–1.50) 0.15
Staphylococcal infection 2.0 (0.75–5.33) 0.17
Streptococcal infection 1.89 (3.34–10.52) 0.47
Enterococcal infection 0.97 (0.32–2.97) 0.96
BCNIE: blood culture-negative infective endocarditis; CI: confidence inter-
val; COPD: chronic obstructive pulmonary disease; CPB: cardiopulmonary
bypass; DMII: diabetes mellitus type II with or without insulin dependency;
NYHA: New York Heart Association classification.
Table 6: Multivariable logistic regression analysis for 30-day
mortality
Characteristics Odds ratio (95% CI) P-value
Preoperative dialysis dependency 22.75 (4.79–108.14) <0.001
Ejection fraction under 30% 17.91 (3.27–98.01) <0.001
Stroke within 14 days prior to operation 5.21 (1.28–21.2) 0.021
CI: confidence interval.
ADULT CARDIAC
5A. Yousif et al. / Interactive CardioVascular and Thoracic Surgery
continuity, the anterior leaflet of the mitral valve and the muscu-
lar tissue of the left ventricular outflow tract. This tissue support
allows for filling the large tissue spaces left after wide debride-
ment, which prosthetic stented or stentless conduits cannot.
Second, their superior haemodynamics, presumed bacterial re-
sistance, low incidence of reinfection, the avoidance of warfarin-
related complications and very low thrombotic event rates.
Thus, all these advantages make the allograft an ideal substitute
with good clinical outcomes [14–16].
However, relatively young patients may face reoperations in
the long run due to structural valve deterioration or calcification
of the cryopreserved allograft, which is a concern [12,17,18].
Despite this drawback of structural valve degeneration, we be-
lieve that the abovementioned advantages, including infection
control and mitigation of IE-related mortality, outweigh this
long-term risk. Moreover, in the case of allograft degeneration,
valve-in-valve transcatheter aortic valve replacement may then
offer a realistic solution especially in older patients [19,20].
The second goal of this study was to find factors associated
with the 30-day mortality. We found that preoperative dialysis-
dependent patients with aortic root endocarditis were almost 23
times more likely to die within 30 days of postoperative hospital
stay than those who were not dialysis dependent. The reason for
this highly significant association is multifactorial. First, dialysis-
dependent patients are classified under chronic reno-cardiac dis-
ease type 4, which is characterized by accelerated ischaemic and
calcified valvular heart disease. In addition, chronic pressure and
volume overload will eventually deteriorate the left ventricular
function [21]. Second, dialysis-dependent patients are prone to
staphylococcal infections, sepsis, thrombosis and infective endo-
carditis due to the frequent use of vascular access devices [22,
23]. These factors are known to portend a higher 30-day mortal-
ity as well [1,16–19]. Finally, acute renal failure is strongly related
to the severity of postoperative haemodynamic deterioration
caused by cardiogenic- or septic shock. Therefore, the surgical
treatment for bacterial endocarditis in these patients is more de-
manding due to extensive comorbid conditions. In spite of these
complex circumstances and higher operative risk, however, the
guidelines still recommend adhering to the accepted indications
for surgical treatment of infective endocarditis [24,25].
Another strong incremental factor associated with the 30-day
mortality is recent stroke within 14 days prior to operation.
These patients with recent stroke without intracranial bleed-
ing were 5 times more likely to die within 30 days of hospital
stay than those without preoperative neurological event. This
risk factor not only influences the proper timing of surgical in-
tervention but also the choice of prosthesis. Okita et al. [26]
retrospectively investigated the effect of the timing of surgery
for active IE in patients with cerebral complications. In 568
patients, non-haemorrhagic cerebral infarction was present in
118 patients, 54 patients had intracranial haemorrhage and
396 had no cerebral event (control group). Delayed surgery of
more than 2 weeks after cerebral infarction, resulted in a
higher incidence of hospital death compared to those who
underwent surgery within 7 days. In contrast, patients with in-
tracranial haemorrhage who underwent surgery within 7 days
had a higher incidence of hospital death compared to those,
in whom surgery was delayed for more than 8 days. They con-
cluded that early surgery in active IE patients with cerebral in-
farction is safe. Delahaye et al. [27] concluded that there is no
benefit and even potential harm in delaying surgery. So, there
is substantial evidence that early operation in IE is beneficial,
unless the patient suffers major intracranial bleeding or severe
neurological deficits. Finally, this comorbidity also justifies the
use of allografts even in younger patients regarding the risks
associated with anticoagulation in the early postoperative
period.
Finally, in the perioperative period, 6 patients needed an
extracorporeal life support system (ECLS) as a temporary cir-
culatory and respiratory support. They suffered from refrac-
tory septic shock with profound left ventricular impairment.
They had no lactate clearance, mixed venous saturation (Svo2)
<55%, cardiac index <2 l/min/m
2
, mean arterial pressure
<65 mmHg in spite of maximum vasoactive inotropic support
and adequate antibiotic treatment. These highly critical clini-
cal circumstances urged us to implant the ECLS as ultima ratio
therapy in an attempt to restore the oxygenation to the tissue,
Figure 2: (A) Freedom from reintervention adjusted for competing risk with mortality. (B) Freedom from re-endocarditis adjusted for competing risk with mortality.
6A. Yousif et al. / Interactive CardioVascular and Thoracic Surgery
to enhance the circulation and restraining the adverse effects
of cardiac depression and vasoplegia. However, our experi-
ence shows that, even though ECLS is highly effective in bridg-
ing the patient from the operation room to the ICU, 5 of the 6
patients could not be weaned from the ECLS and died. Only 1
patient, who received his ECLS preoperatively, survived. This
poor survival coincides with those reported by others and
confirms that the role of ECLS in refractory septic shock is still
very limited or even futile [28–30].
Strengths and limitations
The strength of this study is that it describes the dedicated ap-
proach with cryopreserved allograft as the conduit of choice for
aortic valve endocarditis with annular abscess formation. On the
other hand, due to the retrospective nature and the lack of rou-
tine structured follow-up in our clinic, a reasonable risk factor
analysis for the long-term mortality was not feasible, nor were
details of long-term valve function available.
CONCLUSIONS
In aortic root endocarditis with abscesses formation, cryopre-
served allografts exhibit excellent clinical performance with a low
rate of reinfection and reintervention, which makes its use as
valve replacement a very desirable option, particularly in the set-
ting of reoperation and or multiple reoperations. Preoperative di-
alysis dependency, ejection fraction under 30% and stroke within
14 days prior to operation were incremental factors associated
with the 30-day mortality.
SUPPLEMENTARY MATERIAL
Supplementary material is available at ICVTS online.
Conflict of interest: none declared.
Data availability
All relevant data are within the manuscript and its Supporting
Information files.
Author contributions
Afram Yousif: Conceptualization; Data curation; Formal analysis;
Methodology; Writing—original draft; Writing—review & editing. Khaldoun
Ali: Writing—review & editing. Marcel Anssar: Writing—review & editing.
Wolfgang Harringer: Formal analysis; Writing—review & editing. Aschraf
El-Essawi: Conceptualization; Formal analysis; Methodology; Supervision;
Writing—original draft; Writing—review & editing. Rene´ Brouwer:
Conceptualization; Formal analysis; Methodology; Supervision; Writing—re-
view & editing.
Reviewer information
Interactive CardioVascular and Thoracic Surgery thanks Satsuki Fukushima,
Mikalai Shchatsinka and the other anonymous reviewer(s) for their contribu-
tion to the peer review process of this article.
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