Sex‐related differences in left ventricular assist device utilization and outcomes: results from the PCHF‐VAD registry

Abstract

Aims
Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort.

Methods and results
This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure, bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess associations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant, women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2 (55% vs. 41%, P = 0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P = 0.001). Mean age was comparable (52.1 vs. 53.4 years, P = 0.33), and median follow-up duration was 344 [range 147–823] days for women and 435 [range 190–816] days for men (P = 0.40). No significant sex-related differences were found in all-cause mortality (hazard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50–1.27]). Female LVAD patients had a lower risk of ventricular arrhythmias (HR 0.56, 95% CI [0.33–0.95]) but more often experienced right ventricular failure. No significant sex-related differences were found in other outcomes.

Conclusions
In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implantation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in female patients is warranted.

Full text

Sex-related differences in left ventricular assist device
utilization and outcomes: results from the PCHF-VAD
registry
Sumant P. Radhoe
1
, Nina Jakus
2
, Jesse F. Veenis
2
, Philippe Timmermans
3
, Anne-Catherine Pouleur
4,5
,
Pawel Rubís
6
, Emeline M. Van Craenenbroeck
7
, Edvinas Gaizauskas
8
, Eduardo Barge-Caballero
9
,
Stefania Paolillo
10
, Sebastian Grundmann
11
, Domenico D’Amario
12
, Oscar Ö. Braun
13
, Aggeliki Gkouziouta
14
,
Ivo Planinc
2
, Jana Ljubas Macek
2
, Bart Meyns
15
, Walter Droogne
3
, Karol Wierzbicki
16
, Katarzyna Holcman
6
,
Andreas J. Flammer
17
, Hrvoje Gasparovic
18
, Bojan Biocina
18
, Davor Milicic
2
, Lars H. Lund
19
,
Frank Ruschitzka
17
, Jasper J. Brugts
1
*and Maja Cikes
2
1
Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
2
Department of Cardiovascular Diseases,
University of Zagreb School of Medicine and University Hospital Center Zagreb, Zagreb, Croatia;
3
Department of Cardiology, University Hospital Leuven, Leuven, Belgium;
4
Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc, Brussels, Belgium;
5
Pôle de Recherche Cardiovasculaire (CARD), Institut de
Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Louvain, Belgium;
6
Department of Cardiac and Vascular Diseases Krakow, Jagiellonian
University Medical College, John Paul II Hospital, Krakow, Poland;
7
Antwerp University Hospital, Antwerp, Belgium;
8
Clinic of Cardiac and Vascular Diseases, Faculty of
Medicine, Vilnius University, Vilnius, Lithuania;
9
INIBIC, CIBERCV, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain;
10
Department of Advanced Biomedical
Sciences, Federico II University of Naples, Naples, Italy;
11
Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany;
12
Fondazione
Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy;
13
Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden;
14
Onassis Cardiac Surgery Centre, Athens, Greece;
15
Department of Cardiac Surgery, University Hospital Leuven, Leuven, Belgium;
16
Department of Cardiovascular Surgery
and Transplantology, Institute of Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland;
17
Clinic for Cardiology, University Hospital Zurich,
Zurich, Switzerland;
18
Department of Cardiac Surgery, University of Zagreb School of Medicine and University Hospital Center Zagreb, Zagreb, Croatia; and
19
Department of
Medicine, Karolinska Institute, Stockholm, Sweden
Abstract
Aims Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly con-
fined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization
and outcomes in a contemporary European LVAD cohort.
Methods and results This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The
primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure,
bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess as-
sociations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant,
women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2
(55% vs. 41%, P= 0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P= 0.001). Mean
age was comparable (52.1 vs. 53.4 years, P= 0.33), and median follow-up duration was 344 [range 147–823] days for women
and 435 [range 190–816] days for men (P= 0.40). No significant sex-related differences were found in all-cause mortality (haz-
ard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50–1.27]). Female LVAD patients had a lower risk of
ventricular arrhythmias (HR 0.56, 95% CI [0.33–0.95]) but more often experienced right ventricular failure. No significant
sex-related differences were found in other outcomes.
Conclusions In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implan-
tation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the
proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients
were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in
female patients is warranted.
Keywords Advanced heart failure; Left ventricular assist device; Utilization; Sex; Survival
Received:
23
June
2022
; Revised:
5
October
2022
; Accepted:
27
November
2022
ORIGINAL ARTICLE
© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any me-
dium, provided the original work is properly cited and is not used for commercial purposes.
ESC HEART FAILURE
ESC Heart Failure 2023; 10: 1054–1065
Published online 22 December 2022 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ehf2.14261

*Correspondence to: Jasper J. Brugts, Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein
40
,
3015
GD
Rotterdam, The Netherlands. Email: j.brugts@erasmusmc.nl
Sumant P. Radhoe, Nina Jakus, Jasper J. Brugts and Maja Cikes contributed equally.
Introduction
Both men and women are frequently affected by heart failure
(HF), and in both sexes, HF is strongly associated with mor-
bidity and mortality.
1,2
However, several sex-related differ-
ences exist, such as the distribution of HF phenotypes and
the aetiology of HF.
2–4
Although the overall lifetime risk of de-
veloping HF is comparable between men and women, women
are underrepresented in HF trials.
1,5-7
Additionally, women
are less likely to be treated with guideline-recommended
drugs. Reports on potential underutilization of device thera-
pies such as implantable cardioverter-defibrillator or cardiac
resynchronization therapy in women have been
inconsistent.
7-14
Even though it is suggested that women
make up approximately one-third of the advanced HF popula-
tion, several studies have shown lower utilization of left ven-
tricular assist devices (LVADs) in women.
15-18
Furthermore,
studies investigating sex-related differences in LVAD out-
comes provided conflicting results. Analyses of large US and
European LVAD registries demonstrated worse clinical out-
comes in women, whereas a smaller study and a
meta-analysis showed similar survival for women and
men.
15,16,19-21
However, these previous studies contained only
a very small proportion of the newest and currently predom-
inant HeartMate 3 LVADs and primarily included data on US
patients. Improving our understanding of sex differences in
present-day European LVAD management is necessary to fur-
ther enhance LVAD care. Therefore, this analysis aimed to as-
sess sex-related differences in LVAD utilization and outcomes
in a contemporary European cohort of LVAD patients.
Methods
The methods of the observational PCHF-VAD registry have
been described previously.
22
Briefly, continuous-flow LVAD
patients were included from 13 European HF tertiary referral
centres by HF specialists—alumni of the Postgraduate Course
in Heart Failure (PCHF) of the Heart Failure Association of the
European Society of Cardiology and the European Heart
Academy, forming the PCHF-VAD registry. All participating
centres acquired approval from the local ethics review boards
(predominantly, a waiver of informed consent was obtained
by the individual centres). The patient baseline (time of im-
plantation) and outcome data were recorded and managed
using REDCap (Research Electronic Data Capture) electronic
data capture tools—a secure, web-based application,
23
hosted at the University of Zagreb School of Medicine, serv-
ing as the data-coordinating centre.
At the moment of this analysis, 583 patients implanted
with a durable ventricular assist device between December
2006 and January 2020 were included in the registry. Patients
with a pulsatile device (n= 4) or biventricular assist device
(n= 11), as well as patients aged <18 years (n= 6), were ex-
cluded from this analysis. In total, 562 patients were included
in this analysis.
The primary outcome was all-cause mortality. Secondary
outcomes included heart transplantation, weaning from
LVAD support, hospitalization for HF, right ventricular (RV)
failure (acute and chronic), LVAD-related infection requiring
systemic antibiotics, non-fatal thromboembolic events, intra-
cranial bleeding, non-intracranial bleeding, LVAD exchange,
and the haemocompatibility score (HCS).
Haemocompatibility score
To analyse the aggregate burden of haemocompatibility-
related adverse events (HRAEs), the HCS was calculated
for all patients. Each HRAE received a points score, based
on its clinical relevance (Table S
1
). The HCS was calculated
for each patient by summing up all points associated with
all HRAEs experienced by the patient during the follow-up
period.
24
Statistical analysis
Continuous data are expressed as mean ± standard deviation
or median and interquartile range (IQR) for non-normally dis-
tributed data and were compared between men and women
by the Student’s t-test or the Mann–Whitney Utest. Categor-
ical data are expressed as counts and percentages and were
compared by the Pearson’sχ
2
test.
Cumulative survival was assessed using the Kaplan–Meier
method and was compared between men and women using
the log-rank test. Cox proportional hazards models were used
to calculate hazard ratios (HRs) and corresponding 95% confi-
dence intervals (CIs) for female vs. male sex for the different
outcomes. For the survival analyses, the time of LVAD implan-
tation was considered as the index date. The follow-up dura-
tion was defined as time to last contact, heart transplanta-
tion, weaning from LVAD support, or death, whichever
occurred first.
For the main analysis, a multivariable Cox regression
model was used to test whether sex was associated with
the outcomes. The association between sex and outcomes
LVAD utilization and outcomes according to sex 1055
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

was adjusted for age, Interagency Registry for Mechanically
Assisted Circulatory Support (INTERMACS) profile, baseline
creatinine serum levels, need for mechanical circulatory sup-
port prior to LVAD implantation, need for vasopressor use
prior to LVAD implantation, and the LVAD implant date
quartile.
Additionally, a sensitivity analysis was performed to adjust
the association between all-cause mortality and sex for base-
line covariates that were selected in a forward stepwise Cox
proportional hazards model. Age, cardiac implantable elec-
tronic devices (including implantable cardioverter-defibrilla-
tor or cardiac resynchronization therapy) status; heart rate,
LVAD type, LVAD intention, INTERMACS profile, aetiology of
HF, known history of chronic kidney disease, atrial fibrilla-
tion/flutter, or ventricular arrhythmias, significant ventricular
arrhythmias pre-LVAD surgery, prior cardiac surgery, concom-
itant procedure with LVAD implant, life support pre-LVAD
surgery, diuretic use, beta-blocker use, ivabradine use, miner-
alocorticoid receptor antagonist use, vasopressor use, ultrafil-
tration, mechanical ventilation, creatinine values, left ventric-
ular (LV) internal dimension at end-diastole, and LVAD
implant date quartile were assessed in a forward stepwise se-
lection process with a significance level of 0.05 and 0.10 for
entry and removal thresholds, respectively. Following this
process, the baseline covariates that came out significant
were used in a Cox proportional hazard model for the sec-
ondary outcomes.
The number of missing data in the variables mentioned
above is shown in Table S
2
. Variables with <30% missing
data were imputed using multiple imputation, whereas those
with a larger proportion of missing data were not included in
this analysis. If the missing variables showed a monotone pat-
tern of missing values, the monotone method was used. Oth-
erwise, an iterative Markov chain Monte Carlo method was
used with a number of 10 iterations. A total of five imputa-
tions was performed, and the pooled data were analysed.
The imputed data were only used for the multivariable anal-
ysis. A two-sided P-value of 0.05 or lower was considered sta-
tistically significant. All statistical analyses were performed
using Statistical Package for Social Sciences, Version 25.0
(SPSS Inc., Chicago, IL, USA).
Results
In this analysis, a total of 562 patients with a mean age of
53.1 ± 12.0 years were included. The cohort included 457
(81.3%) male and 105 (18.7%) female patients. The baseline
characteristics are shown in Table
1
. A higher proportion of
women were critically ill at the time of LVAD implantation
as women were more often in INTERMACS profile 1 or 2
(55.3% vs. 41.2%, P= 0.009) and more often in need of me-
chanical circulatory support pre-LVAD implantation (39.2%
vs. 23.0%, P= 0.001). Serum creatinine levels were lower
and LV size was smaller in women. Additionally, women less
often had diabetes mellitus or atrial fibrillation or flutter at
baseline.
Survival
Women and men were followed for a median period of 344
[IQR 147–823] and 435 [IQR 190–816] days, respectively
(P= 0.40). No differences were observed in the crude
all-cause mortality between men and women, as shown in
Figure
1
. During the entire follow-up period, 29% of the male
and 21% of the female patients died (P= 0.084). Female pa-
tients were numerically less likely to die during follow-up, but
this difference was not statistically significant after adjust-
ments for age, INTERMACS profile, creatinine serum levels,
preoperative need for mechanical circulatory support or va-
sodilator use, and the quartiles of date of LVAD implantation
(HR 0.79, 95% CI [0.50–1.27]; Table
2
). The causes of death
were not different between men and women and are pre-
sented in Figure
2
.
Secondary endpoints
No sex-related differences were observed in the proportion
of patients undergoing heart transplantation (HR 1.01, 95%
CI [0.70–1.46]; Figure
1
). Numerically, women were signifi-
cantly more often weaned from LVAD support, but this was
not statistically significant after multivariable adjustments
(HR 3.10, 95% CI [0.68–14.1]; Table
2
). Peripartum cardiomy-
opathy and dilated cardiomyopathy were the most frequent
causes of HF in women who recovered from LVAD support
(Table S
3
). The results from the competing outcome analysis
are shown in Figure
3
.
Female sex was associated with a significantly lower crude
and adjusted risk of ventricular arrhythmias post-LVAD im-
plant (adjusted HR 0.56, 95% CI [0.33–0.95]; Table
2
). Female
patients had a higher incidence of RV failure, although with-
out statistically significant increase in risk thereof (HR 1.57,
95% CI [1.00–2.49], P= 0.053).
No significant differences between men and women were
found in the occurrence of pump thrombosis, non-fatal
thromboembolic events, or bleeding (Table
2
). A small, non-
significant difference between men and women was found
in the median HCS, as shown in Figure
4
. Furthermore, the
risk of HF hospitalizations, new-onset atrial fibrillation or flut-
ter, and LVAD-related infections requiring antibiotics was sim-
ilar for men and women (Table
2
).
1056 S.P. Radhoe et al.
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

Table 1 Baseline characteristics
Overall population
(n= 562)
Men
(n= 457)
Women
(n= 105) P-value
Age, years 53 ± 12 53 ± 12 52 ± 12 0.33
Geographical area
Northwest Europe (the Netherlands, Belgium, and Germany) 373 (66.4) 292 (63.9) 81 (77.1) 0.01
Southeast Europe (Croatia, Poland, Lithuania, Italy, Spain, and
Greece)
189 (33.6) 165 (36.1) 24 (22.9)
Quartiles of date of LVAD implant
1st quartile (6 Dec 2006–29 Oct 2012) 143 (25.4) 110 (24.1) 33 (31.4) 0.41
2nd quartile (30 Oct 2012–4 Aug 2015) 143 (25.4) 121 (26.5) 22 (21.0)
3rd quartile (5 Aug 2015–16 Apr 2017) 139 (24.7) 114 (24.9) 25 (23.8)
4th quartile (17 Apr 2017–28 Jan 2020) 137 (24.4) 112 (24.5) 25 (23.8)
ICD status 0.34
No ICD 294 (53.3) 235 (52.2) 59 (57.8)
Primary prevention 180 (32.6) 147 (32.7) 33 (32.4)
Secondary prevention 78 (14.1) 68 (15.1) 10 (9.8)
CRT status
No CRT 406 (74.1) 325 (72.9) 81 (79.4) 0.12
CRT-P carrier 14 (2.6) 14 (3.1) 0 (0.0)
CRT-D carrier 128 (23.4) 107 (24.0) 21 (20.6)
Heart rate, b.p.m. 83.3 ± 19.0 82.5 ± 17.8 87.1 ± 23.3 0.072
SBP, mmHg 99.5 ± 13.9 100.0 ± 14.1 97.7 ± 13.0 0.16
DBP, mmHg 64.2 ± 10.9 64.4 ± 10.5 63.2 ± 12.2 0.32
BMI, kg/m
2
25.9 ± 4.6 26.1 ± 4.5 24.9 ± 5.3 0.025
LVAD type
HeartMate 2 265 (47.2) 215 (47.0) 50 (47.6) 0.82
HeartWare HVAD 119 (21.2) 94 (20.6) 25 (23.8)
HeartMate 3 157 (27.9) 130 (28.4) 27 (25.7)
Other 21 (3.7) 18 (3.9) 3 (2.9)
LVAD destination
BTT 356 (66.8) 292 (67.1) 64 (65.3) 0.081
BTD 90 (16.9) 67 (15.4) 23 (23.5)
DT 87 (16.3) 76 (17.5) 11 (11.2)
INTERMACS profile
1 90 (16.5) 61 (13.7) 29 (28.2) 0.004
2 150 (27.4) 122 (27.5) 28 (27.2)
3 176 (32.2) 149 (33.6) 27 (26.2)
4–7 131 (23.9) 112 (25.2) 19 (18.4)
Aetiology of heart failure
Dilated cardiomyopathy 247 (44.0) 204 (44.6) 43 (41.0) <0.001
Ischaemic cardiomyopathy 256 (45.6) 211 (46.2) 45 (42.9)
Hypertrophic cardiomyopathy 9 (1.6) 7 (1.5) 2 (1.9)
Toxic cardiomyopathy 15 (2.7) 6 (1.3) 9 (8.6)
Non-compaction cardiomyopathy 3 (0.5) 3 (0.7) 0 (0.0)
Valvular disease 6 (1.1) 6 (1.3) 0 (0.0)
Myocarditis 12 (2.1) 9 (2.0) 3 (2.9)
Peripartum cardiomyopathy 2 (0.4) 0 (0.0) 2 (1.9)
Congenital/genetic 6 (1.1) 6 (1.3) 0 (0.0)
Other 6 (1.1) 42 (9.2) 17 (16.2)
Comorbidities
Arterial hypertension 128 (22.8) 105 (23.0) 23 (21.9) 0.81
Diabetes mellitus 114 (20.3) 100 (21.9) 14 (13.3) 0.049
Chronic kidney disease 137 (24.4) 117 (25.6) 20 (19.0) 0.16
Coronary artery disease 139 (24.7) 120 (26.3) 19 (18.1) 0.080
Prior MI 211 (37.5) 178 (38.9) 33 (31.4) 0.15
Prior coronary revascularization 170 (30.2) 141 (30.9) 29 (27.6) 0.52
COPD 44 (7.8) 40 (8.8) 4 (3.8) 0.089
Atrial fibrillation/flutter 173 (30.8) 155 (33.9) 18 (17.1) 0.001
Ventricular arrhythmias 153 (27.2) 127 (27.8) 26 (24.8) 0.53
Cerebrovascular events 41 (7.3) 34 (7.4) 7 (6.7) 0.78
Significant ventricular arrhythmias pre-LVAD implant
None 308 (65.5) 242 (63.2) 66 (75.9) 0.093
1 episode 78 (16.6) 64 (16.7) 14 (16.1)
2 episodes 34 (7.2) 30 (7.8) 4 (4.6)
3 episodes 18 (3.8) 17 (4.4) 1 (1.1)
≥4 episodes 32 (6.8) 30 (7.8) 2 (2.3)
Prior cardiac surgery 75 (13.3) 65 (14.2) 10 (9.5) 0.20
(Continues)
LVAD utilization and outcomes according to sex 1057
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

Sensitivity analysis
The results of the sensitivity analysis, in which the association
between sex and the primary and secondary outcomes was
adjusted using a forward stepwise Cox regression model,
are shown in Table S
4
. Similar to the main analysis, there
was no significant difference in all-cause mortality. However,
female sex was significantly associated with RV failure post-
LVAD implantation and weaning from LVAD support.
Discussion
In this contemporary European LVAD registry reflecting
real-world clinical practice at multiple HF tertiary referral
centres, we demonstrated that fewer women than men
underwent LVAD implantation (19% vs. 81%, respectively).
Also, women were implanted at a more advanced stage and
were more critically ill pre-LVAD surgery; nevertheless, no
significant survival differences were observed between men
and women. Furthermore, only minor sex-related differences
in LVAD-related outcomes were observed, with women less
often at risk of ventricular arrhythmias, more often suffering
from RV failure, and more often having explant for recovery
(albeit rarely altogether).
Previous studies have investigated sex differences in the
utilization and outcomes of LVAD therapy. However, most of
these studies have been performed in the United States,
reflected an earlier period, and included almost exclusively
HeartWare HVAD or HeartMate 2 devices.
15,16,19-21
As op-
posed to these earlier studies, the current study included a
relatively large number of patients with a HeartMate 3 de-
vice, and this registry therefore provides unique insights into
the contemporary LVAD management at European tertiary
referral centres using state-of-the-art LVADs.
25,26,27
Potential left ventricular assist device
underutilization
Women remain underrepresented in large pharmacological
clinical HF trials, as well as in LVAD clinical trials.
7,25
Currently,
less women than men receive an LVAD, as demonstrated in
this registry as well as in other studies, with the proportion
of female patients spanning from 20.8% to 23.2%.
15–17
De-
spite several large registries showing that women make up
approximately one-third of the advanced and worsening HF
populations, only 19% of our cohort were female, suggesting
potential LVAD underutilization in female patients.
18,28
Sev-
eral reasons might contribute to the lower utilization of
LVADs in women. Firstly, women are more frequently diag-
Table 1 (continued)
Overall population
(n= 562)
Men
(n= 457)
Women
(n= 105) P-value
Concomitant procedure with LVAD implant 99 (17.6) 82 (17.9) 17 (16.2) 0.67
Mechanical circulatory support pre-LVAD implant
None 401 (74.0) 339 (77.0) 62 (60.8) 0.007
ECMO 40 (7.4) 30 (6.8) 10 (9.8)
Temporary LVAD 5 (0.9) 5 (1.1) 0 (0.0)
Temporary RVAD 1 (0.2) 1 (0.2) 0 (0.0)
Temporary BiVAD 2 (0.4) 2 (0.5) 0 (0.0)
IABP 73 (13.5) 51 (11.6) 22 (21.6)
Other 20 (3.7) 12 (2.7) 8 (7.8)
Medications
Diuretic 454 (91.0) 374 (91.7) 80 (87.9) 0.26
Beta-blocker 299 (64.4) 252 (65.5) 47 (59.5) 0.31
ACEi/ARB 213 (44.9) 176 (44.8) 37 (45.7) 0.88
MRA 315 (72.1) 265 (73.8) 50 (64.1) 0.08
Ivabradine 45 (10.9) 38 (11.1) 7 (9.7) 0.73
Inotrope 305 (66.6) 243 (65.1) 62 (72.9) 0.17
Laboratory values
Creatinine, μmol/L 127.1 ± 56.0 131.4 ± 55.2 108.1 ± 55.8 <0.001
Bilirubin, μmol/L 24.3 ± 20.5 24.8 ± 21.0 22.2 ± 18.5 0.30
Echocardiographic data
LVIDd, mm 70.7 ± 12.5 72.3 ± 12.3 63.9 ± 11.3 <0.001
LVIDd/BSA ratio 36.5 ± 6.8 36.4 ± 6.9 36.9 ± 6.6 0.61
LVEF, % 19.4 ± 7.5 19.2 ± 7.6 20.3 ± 6.8 0.24
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; b.p.m., beats per minute; BiVAD, biventricular assist
device; BMI, body mass index; BSA, body surface area; BTD, bridge to decision; BTT, bridge to transplant; COPD, chronic obstructive pul-
monary disease; CRT, cardiac resynchronization therapy; CRT-D, CRT-defibrillator; CRT-P, CRT-pacing; DBP, diastolic blood pressure; DT,
destination therapy; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; ICD, implantable cardioverter-defi-
brillator; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; LVAD, left ventricular assist device; LVEF, left
ventricular ejection fraction; LVIDd, left ventricular internal dimension at end-diastole; MI, myocardial infarction; MRA, mineralocorticoid
receptor antagonist; RVAD, right ventricular assist device; SBP, systolic blood pressure.
1058 S.P. Radhoe et al.
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

Figure 1 Kaplan–Meier plots of time to (A) all-cause mortality, (B) heart transplantation (censored for death), and (C) weaning from left ventricular
assist device (LVAD) (censored for death) according to sex.
LVAD utilization and outcomes according to sex 1059
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

nosed with HF with preserved ejection fraction, in whom
LVAD support is not indicated.
29
Secondly, the lower inclusion
rate of women in LVAD trials has led to a gap of evidence in
the effectiveness of LVAD support in women, which might
have caused a difference in the utilization of LVAD therapy.
Additionally, in the pulsatile-flow device era, female patients
were deemed less suited for implantation of the larger
pumps due to their smaller intrathoracic volume.
15,20
Thus,
Table 2 Frequency (proportion) and hazard ratios for the studied endpoints
Overall population
(n= 562)
Men
(n= 457)
Women
(n= 105)
P-
value
Unadjusted HR
[95% CI]
Adjusted HR
[95% CI]
a
All-cause mortality 156 (27.8) 134 (29.3) 22 (21.0) 0.084 0.75 [0.48–1.18] 0.79 [0.50–1.27]
HF hospitalization 108 (20.8) 85 (20.1) 23 (24.0) 0.41 1.16 [0.73–1.86] 1.27 [0.78–2.06]
RV failure 116 (21.4) 87 (19.7) 29 (29.0) 0.041 1.52 [0.98–2.35] 1.57 [1.00–2.49]
Atrial fibrillation/flutter 79 (14.8) 66 (15.2) 13 (13.0) 0.57 0.83 [0.45–1.54] 0.98 [0.52–1.86]
Ventricular arrhythmia 155 (28.4) 137 (30.9) 18 (17.6) 0.008 0.50 [0.30–0.85] 0.56 [0.33–0.95]
LVAD-related infections
requiring AB
188 (34.6) 156 (35.4) 32 (31.4) 0.44 0.84 [0.56–1.25] 0.76 [0.50–1.14]
Non-intracranial bleeding 118 (22.1) 99 (22.7) 19 (19.6) 0.51 0.88 [0.54–1.45] 0.88 [0.53–1.46]
Intracranial bleeding 46 (8.6) 39 (8.9) 7 (7.1) 0.56 0.87 [0.39–1.94] 0.78 [0.32–1.89]
Pump thrombosis 41 (7.6) 38 (8.6) 3 (3.1) 0.06 0.35 [0.11–1.15] 0.38 [0.12–1.26]
Non-fatal thromboembolic
events
56 (10.4) 44 (10.0) 12 (12.2) 0.51 1.21 [0.64–2.29] 1.31 [0.68–2.54]
Weaning from LVAD 9 (1.6) 4 (0.9) 5 (4.8) 0.004 6.07 [1.63–22.62] 3.10 [0.68–14.07]
LVAD exchange 22 (4.1) 18 (4.1) 4 (4.1) 0.98 0.93 [0.31–2.75] 0.85 [0.28–2.61]
Heart transplantation 218 (38.8) 175 (38.3) 43 (41.0) 0.61 1.11 [0.79–1.55] 1.01 [0.70–1.46]
AB, antibiotics; CI, confidence interval; HF, heart failure; HR, hazard ratio; LVAD, left ventricular assist device; RV, right ventricular.
a
Adjusted for age, Interagency Registry for Mechanically Assisted Circulatory Support profile, creatinine serum levels at baseline, preoper-
ative need for life support, preoperative vasodilator use, and quartiles of date of LVAD implantation.
Figure 2 Detailed causes of death stratified by sex. CV, cardiovascular.
1060 S.P. Radhoe et al.
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

for this and potentially other reasons, LVAD therapy may be
less often utilized in women. Furthermore, it has been sug-
gested that women are more likely to decline LVAD support
than men.
30,31
In a multinational European screening study,
women were somewhat less likely to be eligible for LVAD
and/or heart transplantation but considerably less likely to ac-
cept LVAD and/or transplantation if indicated.
32
Additionally,
it could be that physicians and patients wait too long with
the decision to proceed towards LVAD implantation, as
reflected by the strikingly high proportion of women in the
worst INTERMACS profile and the higher need for mechanical
circulatory support in women.
20
Another explanation for the
worse INTERMACS profile and high need for mechanical circu-
latory support in women might be that they are more often
affected by acute disease, which possibly explains their better
renal function, lower prevalence of atrial fibrillation and ven-
tricular arrhythmias prior to LVAD implantation, and smaller
LV size, which possibly reflects less time for remodelling due
to acuteness of disease. Finally, the inconsistencies in current
literature on sex-related differences in LVAD outcomes might
have influenced LVAD implantation rates in women.
15,16,19–21
Outcomes after left ventricular assist device
implantation
Survival differences between male and female LVAD patients
have previously been investigated and inconsistent results
Figure 3 Competing event analysis in (A) men and (B) women. HTx, heart transplantation; LVAD, left ventricular assist device.
Figure 4 Haemocompatibility score according to sex.
LVAD utilization and outcomes according to sex 1061
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

have been reported.
15,16,19–21
The two largest databases, the
United Network for Organ Sharing (UNOS) and INTERMACS
registry, included a combined total of 32 173 LVAD patients,
and both studies demonstrated a higher adjusted mortality
risk for women.
15,16
A smaller European sex-specific analysis
from the European Registry for Patients with Mechanical Cir-
culatory Support (EUROMACS) also demonstrated worse sur-
vival in women.
20
Conversely, a sub-analysis from the Me-
chanical Circulatory Support Research Network as well as a
recently published meta-analysis did not show survival differ-
ences between male and female LVAD recipients.
19,21
In contrast to most of the earlier studies, survival for
women in our study was at least as good as for men despite
a more critically ill state prior to LVAD implantation. This was
reflected by lower INTERMACS profile and higher need for
mechanical circulatory support, which have been associated
with worse outcome.
33,34
The observed discrepancy regard-
ing survival differences may partially be attributed to differ-
ences in the devices studied. Earlier studies including
pulsatile-flow LVADs predominantly demonstrated worse sur-
vival in women.
17
Later studies on sex differences in the
continuous-flow LVAD era mainly incorporated older devices,
whereas 28% of our overall study population had a
HeartMate 3 device implanted. This is a relatively large pro-
portion compared with the UNOS and EUROMACS studies
in which 2.7% and 0.1% of the overall population received a
HeartMate 3, respectively, while the INTERMACS study did
not incorporate any data from HeartMate 3 LVADs.
15,16,20
This is important as the MOMENTUM 3 trial demonstrated
superiority of the HeartMate 3 LVAD in terms of a lower risk
of disabling stroke or reoperation for replacement or removal
due to malfunction and is considered the most contemporary
LVAD in Europe.
25
An additional subgroup analysis of the MO-
MENTUM 3 trial showed comparably favourable outcomes
for men and women, both on the short and long terms.
35,36
The higher proportion of HeartMate 3 devices in our study
may further explain why the risk of bleeding and thromboem-
bolic events was comparable for men and women in our
study as opposed to earlier studies reporting an increased
risk of major bleeding events.
16,20
The HVAD and HeartMate
2 have been associated with higher stroke, pump thrombosis,
and major bleeding rates, which may translate into a higher
mortality risk, as bleeding events and pump thrombosis have
been associated with higher risk of mortality.
20,25,37,38
Several
studies did not find a difference in bleeding risk, and inconsis-
tent results have been reported on whether women are at an
increased risk for thromboembolic events.
16,20,21,39,40
To the
best of our knowledge, we are the first to investigate sex dif-
ferences with regard to HRAE by using the HCS and found no
significant differences between men and women in our
cohort.
In very carefully selected patients with cardiac recovery af-
ter LVAD surgery, weaning from LVAD support can be a viable
option.
41
Similar to a recent INTERMACS registry analysis, our
results demonstrate that women were more likely to recover
from LVAD support.
16
This might be explained by the ob-
served difference in the aetiology of HF, especially due to
the (partial) reversibility of peripartum cardiomyopathy.
42
Additionally, it has been demonstrated that women have
more favourable reverse remodelling on LVAD support com-
pared with men.
43
In line with earlier studies, female LVAD patients showed a
trend towards increased risk of RV failure.
19,20
It has been
suggested that ventricular arrhythmias might explain the in-
creased risk of RV failure in women, but in our study, women
were less often affected by ventricular arrhythmias post-
LVAD implant.
20,44
However, a higher proportion of women
were in INTERMACS profile 1 (28.2% of female vs. 13.7% of
male patients) and supported with extracorporeal membrane
oxygenation (ECMO), which may explain the higher incidence
of RV failure. Furthermore, the smaller LV size of women has
been associated with RV failure through leftward shifting of
the interventricular septum, which increases RV wall stress
and reduces RV contractility, and may therefore also have
contributed to the increased risk of RV failure.
45,46
Limitations
This study has some limitations. Firstly, data missing not at
random might have introduced bias to our results, although
we have used the multiple imputation method to account
for this in the multivariable Cox proportional hazard models.
Secondly, due to its retrospective design, causality could not
be investigated. Thirdly, due to the small number of patients
weaned from LVAD support, our findings on recovery from
LVAD support should be interpreted with caution. Finally, se-
lection bias or misclassification of data might have occurred.
Conclusions
In this cohort of contemporary LVAD patients from multiple
European HF tertiary referral centres, fewer women
underwent LVAD implantation as compared to men. This is
important as the proportion of female LVAD patients was
lower than the proportion of females with advanced HF as re-
ported in previous studies, suggesting underutilization. Fur-
thermore, female patients were referred for LVAD implanta-
tion in an inferior INTERMACS profile, suggesting later
referral for LVAD therapy. Despite a more critically ill state
prior to implantation, LVAD therapy appears at least as ben-
eficial in terms of survival and clinical outcomes in women
as in men. This should reduce the hesitance of referring fe-
male patients for LVAD implantation, thus providing opportu-
nities for improved outcome similar to male patients. Addi-
tional research is needed to investigate whether LVAD
utilization in women is lower than required, why it occurs,
1062 S.P. Radhoe et al.
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

and whether this trend can be diverted to a more upstream
use of LVAD therapy in women.
Conflict of interest
N.J. reports personal fees and non-financial support from
Servier, personal fees from Teva Pharmaceutical Industries,
Krka, SanofiGenzyme, Boehringer Ingelheim, and Bayer, and
non-financial support from Abbott, outside the submitted
work. A.C.P. reports personal fees from Novartis, Bayer, Vifor,
and AstraZeneca, outside the submitted work. I.P. reports
grants and personal fees from Boehringer Ingelheim, per-
sonal fees from Teva Pharmaceutical Industries, Servier, Krka,
and Corvia, and personal fees and non-financial support from
Novartis, Pfizer, Bayer, Sandoz, Abbott, and SanofiAventis,
outside the submitted work. A.J.F. reports personal fees from
Alnylam, Bayer, Boehringer Ingelheim, Fresenius, Imedos Sys-
tems, Medtronic, MSD, Mundipharma, Pierre Fabre, Pfizer,
Roche, Vifor, and ZOLL, and grants and personal fees from
AstraZeneca and Novartis, outside the submitted work. L.H.
L. reports personal fees from Merck, Bayer, Pharmacosmos,
Abbott, Medscape, Myokardia, Sanofi, Lexicon, and Radcliffe
Cardiology, grants and personal fees from Vifor-Fresenius,
AstraZeneca, Boehringer Ingelheim, and Novartis, and grants
from Boston Scientific, outside the submitted work. D.M. re-
ports personal fees from Boehringer Ingelheim, Bayer, Pfizer,
Novartis, AstraZeneca, Novo Nordisk, Teva, and Servier, out-
side the submitted work. F.R. has not received personal pay-
ments by pharmaceutical companies or device manufacturers
in the last 3 years (remuneration for the time spent in activ-
ities, such as participation as steering committee member of
clinical trials and member of the Pfizer Research Award selec-
tion committee in Switzerland, were made directly to the
University of Zurich). The Department of Cardiology (Univer-
sity Hospital of Zurich/University of Zurich) reports research,
educational, and/or travel grants from Abbott, Amgen,
AstraZeneca, Bayer, Berlin Heart, B. Braun, Biosense Webster,
Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim,
Boston Scientific, Bracco, Cardinal Health Switzerland,
Corteria, Daiichi, Diatools AG, Edwards Lifesciences, Guidant
Europe NV (BS), Hamilton Health Sciences, Kaneka Corpora-
tion, Kantar, Labormedizinisches Zentrum, Medtronic, MSD,
Mundipharma Medical Company, Novartis, Novo Nordisk,
Orion, Pfizer, Quintiles Switzerland Sarl, Sahajanand IN,
Sanofi, Sarstedt AG, Servier, SIS Medical, SSS International
Clinical Research, Terumo Deutschland, Trama Solutions, V-
Wave, Vascular Medi cal, Vifor, Wissens Plus, and ZOLL. The re-
search and educational grants do not impact on F.R.’s per-
sonal remuneration. M.C. reports grants and personal fees
from Novartis, grants from Abbott, personalfees from GE
Healthcare, Bayer, Boehringer Ingelheim, AstraZeneca, Teva
Pharmaceutical Industries, Sanofi, and LivaNova, non-finan-
cial support from Corvia, and personal fees and non-financial
support from Pfizer, outside the submitted work. J.J.B. re-
ports personal fees from Abbott, outside the submitted work.
All other authors have no conflict of interest to disclose.
Funding
None.
Supporting information
Additional supporting information may be found online in the
Supporting Information section at the end of the article.
Table S1. Classification of haemocompatibility score.
Table S2. Number (percentage) of missing data.
Table S3. Etiology of heart failure in patients who were
weaned from LVAD support.
Table S4. Numbers and hazard ratios for the endpoints after a
forward stepwise selection process.
References
1. Lloyd-Jones DM, Larson MG, Leip EP,
Beiser A, D’Agostino RB, Kannel WB,
Murabito JM, Vasan RS, Benjamin EJ,
Levy D, Framingham Heart S. Lifetime
risk for developing congestive heart fail-
ure: the Framingham Heart Study. Circu-
lation. 2002; 106 : 3068–3072.
2. Mehta PA, Cowie MR. Gender and heart
failure: a population perspective. Heart.
2006; 92: iii14–iii18.
3. He J, Ogden LG, Bazzano LA, Vupputuri
S, Loria C, Whelton PK. Risk factors for
congestive heart failure in US men and
women: NHANES I epidemiologic
follow-up study. Arch Intern Med. 2001;
161: 996–1002.
4. Masoudi FA, Havranek EP, Smith G, Fish
RH, Steiner JF, Ordin DL, Krumholz HM.
Gender, age, and heart failure with pre-
served left ventricular systolic function.
J Am Coll Cardiol. 2003; 41:217–223.
5. Alehagen U, Ericsson A, Dahlström U.
Are there any significant differences be-
tween females and males in the manage-
ment of heart failure? Gender aspects of
an elderly population with symptoms as-
sociated with heart failure. J Card Fail.
2009; 15:501–507.
6. Bleumink GS, Knetsch AM,
Sturkenboom MC, Straus SM, Hofman
A, Deckers JW, Witteman JC, Stricker
BH. Quantifying the heart failure epi-
demic: prevalence, incidence rate, life-
time risk and prognosis of heart failure:
the Rotterdam Study. Eur Heart J.
2004; 25: 1614–1619.
LVAD utilization and outcomes according to sex 1063
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

7. Lam CSP, Arnott C, Beale AL,
Chandramouli C, Hilfiker-Kleiner D,
Kaye DM, Ky B, Santema BT, Sliwa K,
Voors AA. Sex differences in heart fail-
ure. Eur Heart J.2019;40: 3859–68c.
8. Abrahamyan L, Sahakyan Y,
Wijeysundera HC, Krahn M, Rac VE.
Gender differences in utilization of spe-
cialized heart failure clinics. J Womens
Health (Larchmt).2018;27: 623–629.
9. Galvao M, Kalman J, DeMarco T,
Fonarow GC, Galvin C, Ghali JK,
Moskowitz RM. Gender differences in
in-hospital management and outcomes
in patients with decompensated heart
failure: analysis from the Acute Decom-
pensated Heart Failure National Regis-
try (ADHERE). J Card Fail. 2006; 12:
100–107.
10. Lenzen MJ, Rosengren A, Scholte OP,
Reimer WJ, Follath F, Boersma E, Si-
moons ML, Cleland JG, Komajda M.
Management of patients with heart fail-
ure in clinical practice: differences be-
tween men and women. Heart. 2008;
94:e10.
11. Linde C, Stahlberg M, Benson L, Braun-
schweig F, Edner M, Dahlstrom U,
Alehagen U, Lund LH. Gender, underuti-
lization of cardiac resynchronization
therapy, and prognostic impact of QRS
prolongation and left bundle branch
block in heart failure. Europace.2015;
17: 424–431.
12. Lund LH, Braunschweig F, Benson L,
Stahlberg M, Dahlstrom U, Linde C. As-
sociation between demographic, organi-
zational, clinical, and socio-economic
characteristics and underutilization of
cardiac resynchronization therapy: re-
sults from the Swedish Heart Failure
Registry. Eur J Heart Fail.2017;19 :
1270–1279.
13. Piña IL, Kokkinos P, Kao A, Bittner V,
Saval M, Clare B, Goldberg L, Johnson
M, Swank A, Ventura H, Moe G, Fitz-
Gerald M, Ellis SJ, Vest M, Cooper L,
Whellan D, Investigators H-A. Baseline
differences in the HF-ACTION trial by
sex. Am Heart J. 2009; 158:S16–S23.
14. Veenis JF, Rocca HB, Linssen GC, Erol-
Yilmaz A, Pronk AC, Engelen DJ, van
Tooren RM, Koornstra-Wortel HJ, de
Boer RA, van der Meer P, Hoes AW,
Brugts JJ, CHECK-HF investigators. Im-
pact of sex-specific target dose in chronic
heart failure patients with reduced ejec-
tion fraction. Eur J Prev Cardiol. 2020;
28:957–965.
15. DeFilippis EM, Truby LK, Garan AR,
Givens RC, Takeda K, Takayama H, Naka
Y, Haythe JH, Farr MA, Topkara VK. Sex-
related differences in use and outcomes
of left ventricular assist devices as
bridge to transplantation. JACC Heart
Fail.2019;7: 250–257.
16. Gruen J, Caraballo C, Miller PE,
McCullough M, Mezzacappa C, Ravindra
N, Mullan CW, Reinhardt SW, Mori M,
Velazquez E, Geirsson A, Ahmad T, Desai
NR. Sex differences in patients receiving
left ventricular assist devices for
end-stage heart failure. JACC Heart Fail.
2020; 75:807.
17. Joshi AA, Lerman JB, Sajja AP, Dahiya G,
Gokhale AV, Dey AK, Kyvernitakis A,
Halbreiner MS, Bailey S, Alpert CM,
Poornima IG, Murali S, Benza RL,
Kanwar M, Raina A. Sex-based differ-
ences in left ventricular assist device uti-
lization: insights from the nationwide in-
patient sample 2004 to 2016. Circ Heart
Fail.2019;12 : e006082.
18. Costanzo MR, Mills RM, Wynne J. Char-
acteristics of “Stage D”heart failure: in-
sights from the Acute Decompensated
Heart Failure National Registry Longitu-
dinal Module (ADHERE LM). Am Heart
J. 2008; 155: 339–347.
19. Blumer V, Mendirichaga R, Hernandez
GA, Zablah G, Chaparro SV. Sex-specific
outcome disparities in patients receiving
continuous-flow left ventricular assist
devices: a systematic review and meta-
analysis. ASAIO J.2018;64:440–449.
20. Magnussen C, Bernhardt AM, Ojeda FM,
Wagner FM, Gummert J, de By T,
Krabatsch T, Mohacsi P, Rybczynski M,
Knappe D, Sill B, Deuse T, Blankenberg
S, Schnabel RB, Reichenspurner H. Gen-
der differences and outcomes in left ven-
tricular assist device support: the Euro-
pean Registry for Patients with
Mechanical Circulatory Support. J Heart
Lung Transplant.2018;37:61–70.
21. Meeteren JV, Maltais S, Dunlay SM,
Haglund NA, Beth Davis M, Cowger J,
Shah P, Aaronson KD, Pagani FD, Stulak
JM. A multi-institutional outcome analy-
sis of patients undergoing left ventricu-
lar assist device implantation stratified
by sex and race. J Heart Lung Transplant.
2017; 36:64–70.
22. Cikes M, Jakus N, Claggett B, Brugts JJ,
Timmermans P, Pouleur AC, Rubis P,
Van Craenenbroeck EM, Gaizauskas E,
Grundmann S, Paolillo S, Barge-Cabal-
lero E, D’Amario D, Gkouziouta A,
Planinc I, Veenis JF, Jacquet LM, Houard
L, Holcman K, Gigase A, Rega F,
Rucinskas K, Adamopoulos S, Agostoni
P, Biocina B, Gasparovic H, Lund LH,
Flammer AJ, Metra M, Milicic D,
Ruschitzka F, PCHF-VAD registry. Car-
diac implantable electronic devices with
adefibrillator component and all-cause
mortality in left ventricular assist device
carriers: results from the PCHF-VAD reg-
istry. Eur J Heart Fail.2019;21:
1129–1141.
23. Harris PA, Taylor R, Thielke R, Payne J,
Gonzalez N, Conde JG. Research elec-
tronic data capture (REDCap)—a
metadata-driven methodology and
workflow process for providing transla-
tional research informatics support. J
Biomed Inform. 2009; 42:377–381.
24. Mehra MR. The burden of
haemocompatibility with left ventricular
assist systems: a complex weave. Eur
Heart J.2019;40:673–677.
25. Mehra MR, Uriel N, Naka Y, Cleveland
JC Jr, Yuzefpolskaya M, Salerno CT,
Walsh MN, Milano CA, Patel CB, Hutch-
ins SW, Ransom J, Ewald GA, Itoh A,
Raval NY, Silvestry SC, Cogswell R, John
R, Bhimaraj A, Bruckner BA, Lowes BD,
Um JY, Jeevanandam V, Sayer G, Mangi
AA, Molina EJ, Sheikh F, Aaronson K,
Pagani FD, Cotts WG, Tatooles AJ, Babu
A, Chomsky D, Katz JN, Tessmann PB,
Dean D, Krishnamoorthy A, Chuang J,
Topuria I, Sood P, Goldstein DJ, Investi-
gators M. A fully magnetically levitated
left ventricular assist device—final re-
port. N Engl J Med.2019;380:
1618–16 27.
26. Jakus N, Brugts JJ, Claggett B,
Timmermans P, Pouleur AC, Rubis P,
Van Craenenbroeck EM, Gaizauskas E,
Barge-Caballero E, Paolillo S,
Grundmann S, D’Amario D, Braun OO,
Gkouziouta A, Meyns B, Droogne W,
Wierzbicki K, Holcman K, Planinc I,
Skoric B, Flammer AJ, Gasparovic H,
Biocina B, Lund LH, Milicic D,
Ruschitzka F, Cikes M, PCHF-VAD regis-
try. Improved survival of left ventricular
assist device carriers in Europe accord-
ing to implantation eras—results from
the PCHF-VAD registry. Eur J Heart Fail.
2022; 24: 1305–1315.
27. Radhoe SP, Veenis JF, Jakus N,
Timmermans P, Pouleur A, Rubís P, Van
Craenenbroeck EM, Gaizauskas E,
Barge-Caballero E, Paolillo S,
Grundmann S, D’Amario D, Braun OÖ,
Gkouziouta A, Planinc I, Samardzic J,
Meyns B, Droogne W, Wierzbicki K,
Holcman K, Flammer AJ, Gasparovic H,
Biocina B, Lund LH, Milicic D,
Ruschitzka F, Cikes M, Brugts JJ. How
does age affect outcomes after left ven-
tricular assist device implantation: re-
sults from the PCHF-VAD registry. ESC
Heart Fail. 2022.
28. Ezekowitz J, Mentz RJ, Westerhout CM,
Sweitzer NK, Givertz MM, Pina IL,
O’Connor CM, Greene SJ, McMullan C,
Roessig L, Hernandez AF, Armstrong
PW. Participation in a heart failure clini-
cal trial: perspectives and opportunities
from the VICTORIA trial and VICTORIA
simultaneous registry. Circ Heart Fail.
2021; 14: e008242.
29. Ammar KA, Jacobsen SJ, Mahoney DW,
Kors JA, Redfield MM, Burnett JC Jr,
Rodeheffer RJ. Prevalence and prognos-
tic significance of heart failure stages:
application of the American College of
Cardiology/American Heart Association
heart failure staging criteria in the com-
munity. Circulation. 2007; 115:
1563–1570.
30. Bruce CR, Kostick KM, Delgado ED,
Wilhelms LA, Volk RJ, Smith ML,
McCurdy SA, Loebe M, Estep JD,
Blumenthal-Barby JS. Reasons why eli-
gible candidates decline left ventricular
assist device placement. J Card Fail.
2015; 21: 835–839.
31. Regitz-Zagrosek V, Petrov G, Lehmkuhl
E, Smits JM, Babitsch B, Brunhuber C,
Jurmann B, Stein J, Schubert C, Merz
NB, Lehmkuhl HB, Hetzer R. Heart
transplantation in women with dilated
1064 S.P. Radhoe et al.
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261

cardiomyopathy. Transplantation.2010;
89: 236–244.
32. Lund LH, Trochu JN, Meyns B, Caliskan
K, Shaw S, Schmitto JD, Schibilsky D,
Damme L, Heatley J, Gustafsson F.
Screening for heart transplantation and
left ventricular assist system: results
from the ScrEEning for advanced Heart
Failure treatment (SEE-HF) study. Eur J
Heart Fail.2018;20:152–160.
33. Kirklin JK, Naftel DC, Pagani FD,
Kormos RL, Stevenson LW, Blume ED,
Myers SL, Miller MA, Baldwin JT, Young
JB. Seventh INTERMACS annual report:
15,000 patients and counting. J Heart
Lung Transplant.2015;34: 1495–1504.
34. Shah P, Pagani FD, Desai SS, Rongione
AJ, Maltais S, Haglund NA, Dunlay SM,
Aaronson KD, Stulak JM, Davis MB, Sa-
lerno CT, Cowger JA, Mechanical Circu-
latory Support Research N. Outcomes
of patients receiving temporary circula-
tory support before durable ventricular
assist device. Ann Thorac Surg.2017;
103 :106–112.
35. Goldstein DJ, Mehra MR, Naka Y, Sa-
lerno C, Uriel N, Dean D, Itoh A, Pagani
FD, Skipper ER, Bhat G, Raval N, Bruck-
ner BA, Estep JD, Cogswell R, Milano C,
Fendelander L, O’Connell JB, Cleveland
J, Investigators M. Impact of age, sex,
therapeutic intent, race and severity of
advanced heart failure on short-term
principal outcomes in the MOMENTUM
3 trial. J Heart Lung Transplant.2018;
37:7–14.
36. Mehra MR, Goldstein DJ, Cleveland JC,
Cowger JA, Hall S, Salerno CT, Naka Y,
Horstmanshof D, Chuang J, Wang A,
Uriel N. Five-year outcomes in patients
with fully magnetically levitated vs
axial-flow left ventricular assist devices
in the MOMENTUM 3 randomized trial.
JAMA. 2022; 328: 1233–1242.
37. Lalonde SD, Alba AC, Rigobon A, Ross
HJ, Delgado DH, Billia F, McDonald M,
Cusimano RJ, Yau TM, Rao V. Clinical
differences between continuous flow
ventricular assist devices: a comparison
between HeartMate II and HeartWare
HVAD. J Card Surg.2013;28: 604–610.
38. Stulak JM, Davis ME, Haglund N,
Dunlay S, Cowger J, Shah P, Pagani FD,
Aaronson KD, Maltais S. Adverse events
in contemporary continuous-flow left
ventricular assist devices: a
multi-institutional comparison shows
significant differences. J Thorac
Cardiovasc Surg.2016;151:177–189.
39. Morris AA, Pekarek A, Wittersheim K,
Cole RT, Gupta D, Nguyen D, Laskar
SR, Butler J, Smith A, Vega JD. Gender
differences in the risk of stroke during
support with continuous-flow left ven-
tricular assist device. J Heart Lung Trans-
plant.2015;34:1570–1577.
40. Sherazi S, Kutyifa V, McNitt S, Papernov
A, Hallinan W, Chen L, Storozynsky E,
Johnson BA, Strawderman RL, Massey
HT, Zareba W, Alexis JD. Effect of gen-
der on the risk of neurologic events
and subsequent outcomes in patients
with left ventricular assist devices. Am
J Cardiol.2017;119: 297–301.
41. Dandel M, Weng Y, Siniawski H, Potapov
E, Lehmkuhl HB, Hetzer R. Long-term
results in patients with idiopathic di-
lated cardiomyopathy after weaning
from left ventricular assist devices. Cir-
culation. 2005; 112:I37–I45.
42. Patel H, Madanieh R, Kosmas CE, Vatti
SK, Vittorio TJ. Reversible cardiomyopa-
thies. Clin Med Insights Cardi`ol.2015;
9:7–14.
43. Kenigsberg BB, Majure DT, Sheikh FH,
Afari-Armah N, Rodrigo M, Hofmeyer
M, Molina EJ, Wang Z, Boyce S, Najjar
SS, Mohammed SF. Sex-associated dif-
ferences in cardiac reverse remodeling
in patients supported by contemporary
left ventricular assist devices. J Card
Fail. 2020; 26: 494–504.
44. Garan AR, Levin AP, Topkara V, Thomas
SS, Yuzefpolskaya M, Colombo PC,
Takeda K, Takayama H, Naka Y, Whang
W, Jorde UP, Uriel N. Early
post-operative ventricular arrhythmias
in patients with continuous-flow left
ventricular assist devices. J Heart Lung
Transplant.2015;34: 1611–1616.
45. Anne Dual S, Nayak A, Hu Y, Schmid
Daners M, Morris AA, Cowger J. Does
size matter for female continuous-flow
LVAD recipients? A translational ap-
proach to a decade long question. ASAIO
J. 2022; 68:21–27.
46. Lampert BC, Teuteberg JJ. Right ventric-
ular failure after left ventricular assist
devices. J Heart Lung Transplant.2015;
34:1123–1130.
LVAD utilization and outcomes according to sex 1065
ESC Heart Failure 2023; 10: 1054–1065
DOI: 10.1002/ehf2.14261