Journal of Cardiac Failure Vol. 21 No.

2 2015

Persistent Blood Stream Infection in Patients Supported With a

Continuous-Flow Left Ventricular Assist Device Is Associated
With an Increased Risk of Cerebrovascular Accidents
BARRY H. TRACHTENBERG, MD,1,2 ANDREA M. CORDERO-REYES, MD,1 MOLHAM ALDEIRI, MD,1,3
PAULINO ALVAREZ, MD,1 ARVIND BHIMARAJ, MD,1,2 GUHA ASHRITH, MD,1,2 BARBARA ELIAS, RN,2
ERIK E. SUAREZ, MD,1 BRIAN BRUCKNER, MD,1,2 MATTHIAS LOEBE, MD,1,2 RICHARD L. HARRIS, MD,4 J. YI ZHANG, MD,5
GUILLERMO TORRE-AMIONE, MD, PhD,1,6 AND JERRY D. ESTEP, MD1,2
Houston and Galveston, Texas; and Monterrey, Mexico

ABSTRACT
Background: Common adverse events in patients supported with Continuous-flow left ventricular assist
devices (CF-LVAD) include infections and cerebrovascular accidents (CVA). Some studies have suggested
a possible association between blood stream infection (BSI) and CVA.
Methods and Results: Medical records of patients who received Heartmate II (HMII) CF-LVADs in
2008e2012 at a single center were reviewed. CVA was categorized as either hemorrhagic (HCVA) or
ischemic (ICVA). BSI was divided into persistent (pBSI) and nonpersistent (non-pBSI). pBSI was defined
as BSI with the same organism on repeated blood culture O72 hours from initial blood culture despite
antibiotics. Univariate and multivariate analyses were performed to determine predictors. A total of 149
patients had HMII implanted; 76% were male, and the overall mean age was 55.4 6 13 years. There
were a total of 19 (13%) patients who had CVA (7 HCVA and 12 ICVA) at a median of 295 days (range
5e1,096 days) after implantation. There were a total of 28 (19%) patients with pBSI and 17 (11%)
patients with non-pBSI. Patients with pBSI had a trend toward greater BMI (31 kg/m2 vs 27 kg/m2;
P 5 .09), and longer duration of support (1,019 d vs 371 d; P ! .001) compared with those with
non-pBSI. Persistent BSI was associated with an increased risk of mortality and with all-cause CVA on
multivariate analysis (odds ratio [OR] 5.97; P 5 .003) as well as persistent Pseudomonas aeruginosa
infection (OR 4.54; P 5 .048).
Conclusions: Persistent BSI is not uncommon in patients supported by CF-LVAD and is highly associ-
ated with all-cause CVA and increased all-cause mortality. (J Cardiac Fail 2015;21:119e125)
Key Words: Left ventricular assist device, cerebrovascular accident, Pseudomonas aeruginosa, infection.

Left ventricular assist devices (LVADs) are an estab-

From the 1Houston Methodist DeBakey Heart and Vascular Center,
Houston Methodist Hospital, Houston, Texas; 2Houston Methodist JC Wal-
ter Jr. Transplant Center, Houston Methodist Hospital, Houston, Texas;
3
Department of Cardiology, University of Texas Medical Branch, Galves-
ton, Texas; 4Department of Infectious Diseases, Houston Methodist, Hous-
ton, Texas; 5Department of Neurological Surgery, Houston Methodist,
Houston, Texas and 6Catedra de Cardiologia y Medicina Vascular, Tec-
nologico de Monterrey, Monterrey, Mexico.
Manuscript received May 15, 2014; revised manuscript received
October 21, 2014; revised manuscript accepted October 29, 2014.
Reprint requests: Barry Trachtenberg, MD, 6550 Fannin Street, Suite
1901, Houston, Texas, 77030. Tel: þ1 713-441-2762; Fax: þ1 713-790-
2643. E-mail: btrachtenberg@houstonmethodist.org
See page 124 for disclosure information.
1071-9164/$ - see front matter
Ó 2015 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.cardfail.2014.10.019
lished and growing therapeutic option for patients with
advanced heart failure either as bridge to transplant or
destination therapy, with actuarial survival of w80% at 1
year and w70% at 2 years.1 Despite the major improve-
ments in survival and quality of life in patients supported
with LVADs,2 several hurdles remain. The Interagency
Registry for Mechanically Assisted Circulatory Support
(INTERMACS) reports that only 30% of LVAD patients
are free from any major adverse events at 1 year.1 Infec-
tion,3,4 device malfunction,5 bleeding,6e8 and cerebrovas-
cular accidents (CVA; 11% incidence at 1 year) compose
the majority of complications. Cerebrovascular accidents
have detrimental consequences in any patient population
but are particularly devastating in heart failure patients sup-
ported with LVADs because they may preclude these

119
120 Journal of Cardiac Failure Vol. 21 No. 2 February 2015
patients from candidacy for heart transplantation. In the
general population, antecedent infection and inflammation
are associated with an increased risk of CVA9,10; similarly,
patients with infective endocarditis11,12 are more prone to
develop CVA than the general population.
A few studies have found an increased incidence of CVA
in patients who develop blood stream infection (BSI) while
supported with LVADs.13,14 Most of these studies included
patients with both continuous-flow LVADs (CF-LVADs)
and pulsatile-flow devices, thus limiting the extrapolation
of these studies to contemporary LVAD usage, because
CF-LVADs comprise O95% of current implantations. Pa-
tients with CF-LVADs have lower rates of both infection
and CVA compared with patients who receive pulsatile-
flow LVADs.4 Therefore, it is crucial to explore this associ-
ation specifically in the CF-LVAD population. A recent
pilot study found an association between CVA and any
BSI in patients supported with Heartmate II (HMII; Thora-
tec Corp, Pleasanton, California) LVADs.13 We conducted
a retrospective study to explore these observations further
with the specific aim to determine if persistent BSI (as
opposed to transient BSI) is associated with an increased
risk of all-cause CVA (hemorrhagic and/or ischemic) and
all-cause mortality in patients who underwent HMII im-
plantation at our institution.
Methods
Patient Population
We retrospectively reviewed the charts of consecutive patients
who underwent HMII LVAD implantation from 2008 to 2012
either as bridge to transplant (BTT) or as destination therapy at
our institution. Baseline clinical demographics and laboratory
data as well as medical histories were obtained from medical re-
cords under an approved Institutional Review Board protocol.
Brain computerized tomographic (CT) scans and cerebral angio-
grams, when available, were also reviewed to evaluate for CVA
and mycotic aneurysms, respectively.
Definitions
International normalized ratio (INR) data were collected for the
previous 4 weeks at 6 different time points before the CVA. To
compare INR between groups, mean time from implantation to
CVA was calculated, and this mean was used in the non-CVA
cohort to match both groups for time on VAD support. For patients
without CVA, INR data were collected at 6 time points in the 4
weeks before this matched time point. Lowest and highest INRs
were recorded at the same time points for all patients.
To address the accuracy of blood pressure (BP) measurements
in patients supported on continuous-flow pumps, we used the
following protocol. If radial pulse was palpable, we collected
data from manual cuff systolic and diastolic BP measurements
and calculated mean BP. If radial pulse was not palpable, then
we obtained Doppler opening pressure. Mean BP with the use
of Doppler pressure was calculated as Doppler opening pressure
minus 5 mm Hg. In cases where the presence or absence of radial
pulse was not documented or was indeterminate, echocardiogra-
phy (if available within 7 days of blood pressure recording) was
used to determine presence or absence of aortic valve (AV)
opening. If the AV opened, the systolic and diastolic BPs were
used to calculate a mean BP; otherwise the Doppler pressure
was used. Blood pressure measurements were averaged for a 4-
week period preceding CVA in the CVA cohort. In patients
without CVA, we used the median time from HMII implantation
to event from the CVA cohort and applied the same time period
from which to measure 4 weeks of antecedent BPs to calculate
a mean BP.
BSI was determined by means of laboratory testing per standard
of care at our center, and was divided into persistent (pBSI) and
nonpersistent (non-pBSI). Unfortunately there is no universally
accepted temporal definition of persistent bacteremia. Several
studies have arbitrarily defined it with the use of a 72-hour
period.15,16 We classified BSI a priori as persistent if the same or-
ganism grew in the blood on cultures O72 hours apart despite an-
tibiotics. All other BSI was classified as nonpersistent. All patients
with BSI were treated by an infectious disease specialist with
appropriate antibiotics at the time of infection; patients with recur-
rent LVAD-related infections were treated aggressively with
chronic lifelong oral antibiotics on discharge from the hospital.
CVAs were defined as a clinical neurologic deficit with brain
CT findings that correlated with the deficit.
The anticoagulation protocol for patients with HMII LVADs
consisted of warfarin and aspirin except for those with contraindi-
cation to the medication and/or active bleeding. At our institution,
patients are started on warfarin early after surgery with dose ad-
justments for therapeutic INR 1.8e2.5 without the use of heparin
as a bridge to therapeutic warfarin levels. All patients received
perioperative antibiotic prophylaxis consisting of vancomycin, flu-
conazole, rifampin, and levofloxacin. The duration of device sup-
port was calculated from the implantation date to the date of data
collection, death, or transplantation.
Statistical Analysis
We performed descriptive and inferential statistical analysis. All
continuous variables are presented as mean 6 SD and compared
with the use of Mann-Whitney test or, when more than 2 groups,
Kruskall-Wallis with Dunn post test. All categoric variables are
presented as number and percentage and compared with the use
of Fisher exact test. Univariate logistic regression analysis was
performed, and multivariate analysis included variables with
P values of !.2 to determine predictors of outcomes. Kaplan-
Meier curves were constructed for overall mortality and freedom
from stroke. P values of !.05 were considered to be significant.
Results
There were a total of 153 LVADs implanted from 2008 to
2012. Four patients were excluded because they expired the
day of LVAD implantation; therefore, 149 patients were
included in the final analysis. The mean age of the cohort
was 55.4 6 13 years, 76% were male, and 59% had
ischemic cardiomyopathy (Table 1). The average duration
of support was 642 6 532 days (median 637, range
2e2,015). A total of 45 patients (30%) developed bacter-
emia. Of these, 28 (19%) had pBSI and 17 (11%) had
non-pBSI (Table 1). The mean time to 1st BSI was signifi-
cantly different between pBSI and non-pBSI: 343 6 323
(median 240) days and 146 6 154 (median 58) days, respec-
tively (P 5 .02). All patients in the pBSI group cleared their
 CVA and Infection in LVAD Patients  Trachtenberg et al 121

Table 1. Patient Characteristics

No BSI Persistent BSI Nonpersistent BSI
(n 5 104) (n 5 28) (n 5 17) P Value*
Age (y) 55 6 13 54 6 14 57 6 12 .4
Gender .1
Male 80 (77) 13 (46) 12 (71)
Female 24 (23) 15 (54) 5 (29)
Etiology .7
Ischemic 63 (61) 15 (54) 10 (59)
Nonischemic 41 (39) 13 (46) 7 (41)
BMI (kg/m2) 28 6 7 31 6 7 27 6 7 .07
DM 46 (44) 13 (46) 10 (59) .5
HTN 86 (83) 17 (61) 14 (82) .1
Hyperlipidemia 68 (65) 16 (57) 10 (59) 1.0
Atrial fibrillation 28 (27) 6 (21) 3 (18) 1.0
INR 1.9 6 0.4 1.9 6 0.4 1.9 6 0.9 .9
Lowest INR 1.4 6 0.3 1.4 6 0.3 1.4 6 0.3 .9
Highest INR 2.4 6 0.6 2.5 6 0.6 2.5 6 0.9 .9
Aspirin dose (mg) 98 6 62 81 6 0 81 6 0 .9
Duration of support (d) 585 6 505 (580) 1,019 6 535 (1,091) 371 6 374 (275) !.0001
Baseline pump speed (rpm) 9,162 6 384 9,300 6 704 9,294 6 525 .9
Mean BP (mm Hg)z 81 6 10 81 6 11 80 6 7 .7
Source of infection
Driveline NA 16 (57) 6 (35) .2
CVC NA 4 (14) 0 (0) .2
Urosepsis NA 2 (7) 2 (12) .6
Other NA 6 (21) 9 (53) .04
Days from implantation to BSI NA 343 6 323 (240) 146 6 154 (58) .02
Days from 1st BSI to CVA NA 206 6 228 (115) 1 NA
Days from last BSI to CVA NA 65 6 147 (22) 1 NA
CVA 8 (8) 10 (32) 1 (6) .03
Hemorrhagic 0 (0) 6 (18) 1 (6)
Ischemic 8 (8) 4 (14) 0 (0)
Days from implantation to CVA 222 6 387 (81) 843 6 499 (758) 347 !.0001y

BSI, blood stream infection; BMI, body mass index; DM, diabetes mellitus; HTN, hypertension; INR, international normalized ratio; BP, blood pressure;
CVC, central venous catheter; CVA, cerebrovascular accident.
Values presented as mean 6 SD (median) or n (%).
*Compares persistent BSI vs nonpersistent BSI.
y
Compares persistent BSI vs no BSI.
z
Obtained by Doppler e 5 mm Hg if no pulse noted and by cuff if pulse present.

bacteremia with the initial course of antibiotics, with the
average number of days from 1st positive BSI to negative
being 12 6 13 (median 9). However, the same organism
recurred late, with the average number of days from 1st pos-
itive BSI to recurrent positive BSI with the same organism
being 132 6 191 (median 51). The median time from last
positive BSI to CVA in the pBSI group was 22 days.
As shown in Figure 1, Pseudomonas aeruginosa (n 5 12)
and Staphylococcus aureus (n 5 11) were the most com-
mon organisms identified in our patients. The most com-
mon source of infection was the LVAD driveline, but
there were no significant differences in the source of infec-
tion between the relevant groups (Table 1). Patients with
pBSI had a trend to greater body mass index (31 kg/m2
vs 27 kg/m2; P 5 .09) and longer duration of support
(1,019 6 535 d vs 371 6 374 d; P ! .001) compared
with those with non-pBSI; however, they had no other
major differences in comorbidities, anticoagulation status,
and/or aspirin use.
Nineteen patients (13%) had CVA (7 HCVA and 12
ICVA) at a median of 295 days (range 5e1,990) after im-
plantation. There was a significantly greater number of
CVAs in the pBSI group (10/28) compared with both
the control group (8/104) and the group with non-pBSI
(1/17). Of the 10 CVAs in the pBSI group, 6 were hemor-
rhagic and 4 were ischemic, and those in the control group
were all ischemic (Table 1). Although atrial fibrillation,
pBSI, and Pseudomonas aeruginosa were associated with
all-cause CVA on univariate analysis, only pBSI and Pseu-
domonas aeruginosa were on multivariate analysis (odds
ratio [OR] 5.97 [P 5 .003] and OR 4.54 [P 5 .048], respec-
tively; Table 2). To determine if the association was specific
for Pseudomonas or not, we analyzed non-Pseudomonas in-
fections and found no association with CVA. Of note, INR
and mean BP were not associated with CVA.
Although any BSI showed a trend towards a worsened
survival, pBSI was associated with a statistically significant
decrease in survival compared with no BSI (58% mortality
vs 34%; P 5 .01; Fig. 2). Of the 17 deaths in the pBSI
group, 8 were due to CVA, 4 to sepsis with multisystem or-
gan failure, 3 to cardiac arrest, and 2 to respiratory failure.
Hemorrhagic CVA was associated with 100% mortality at a
median of 19 days (range 0e136 days). Of the 7 patients
who had an HCVA, 6 had pBSI and 1 had non-pBSI. Inter-
estingly, all 7 patients had an antecedent Pseudomonas aer-
uginosa infection.
122 Journal of Cardiac Failure Vol. 21 No. 2 February 2015

aeruginosa infections. The occurrence of a hemorrhagic

CVA in our population was associated with 100%
mortality.
A recent INTERMACS analysis found that driveline
infections are associated with decreased survival in patients
supported with CF-LVADs; sepsis was the most common
cause of death in these patients, and CVA was uncommon.17
Our study further complements those findings by showing
that in patients with pBSI, of which the most common
source was a driveline infection (57%), there was a 7-fold
increase in all-cause CVA. Similarly to the INTERMACS
analysis, we also found an association of decreased survival
in patients with greater infectious burden. Thus, although
all patients with driveline infections have increased mortal-
ity, the presence of bacteremia may lead to different
adverse events and mechanisms of death.
Fig. 1. Prevalence of persistent and non-persistent bloodstream In the present study, pBSI was more associated with CVA
infection (BSI) in our continuous-flow left ventricular assist than with traditional risk factors such as age, atrial fibrilla-
device population and the most common microorganisms present tion, and hypertension. In fact, on multivariate analysis,
in patients in each group. pBSI and the presence of persistent Pseudomonas aerugi-
nosa were the only variables associated with CVA. The
risk of CVA from atrial fibrillation was likely mitigated
Three of the 7 patients with HCVA had a mycotic aneu- by the fact that all patients were on warfarin. It is unclear
rysm as demonstrated on cerebral angiography (Fig. 3) and why hypertension was not linked with CVA in our popula-
underwent urgent neurosurgical intervention; nevertheless, tion. Perhaps this was due to hypervigilance about hyper-
all 3 patients died secondary to the event-related HCVA tension control in our cohort, including frequent clinic
at a mean of 59 6 64 days (median 29, range 12e130) after visits and home monitoring of blood pressure.
repair. Earlier studies have suggested that infections are indeed
a risk factor for CVA in patients supported with
Discussion LVADs13,14,18; to our knowledge, ours is the largest study
to explore the association of BSI and CVA in patients
In this retrospective single-center study, we found that with CF-LVADs (ie, HMII) and the 1st to suggest that the
pBSI in patients with HMII LVADs was associated with persistence of bacteremia could be a potential contributor.
increased mortality and all-cause CVA compared with pa- Our hypothesis for the causative role of persistent bacter-
tients with non-pBSI or no BSI. In addition, we found that emia (in contradistinction to any bacteremia) is supported
the vast majority of hemorrhagic CVA occurred in by the fact that whereas the median time from 1st positive
patients with pBSI, particularly those with Pseudomonas BSI to CVA was long, the median time from last positive
BSI to CVA was short (22 days).
The reason that persistent bacteremia is associated with
CVA, however, is not clearly known and deserves further
Table 2. Factors Associated With All-Cause CVA
exploration. The link between infections and thrombotic
Variable OR CI P Value events is not limited to patients with intracardiac devices.
A recent population study found that patients admitted
Univariate analysis
Gender (male/female) 1.54 0.54e4.4 .421 with community-acquired bacteremia had a significant in-
Age (y) 0.98 0.95e1.02 .311 crease in acute myocardial infarctions or CVAs compared
Hypertension (yes/no) 0.54 0.19e1.56 .256 with the general population or patients hospitalized without
Atrial fibrillation (yes/no) 2.53 0.93e6.88 .049
INR (mean) 1.45 0.6e3.46 .406 bacteremia.19 Interestingly, the incidence of thrombotic
BP (mean) 0.99 0.96e1.02 .494 events was even greater in those patients with infective en-
pBSI (yes/no) 6.91 2.47e17.34 .0001 docarditis, higher number of positive cultures, or greater
Pseudomonas aeruginosa 7.38 1.99e22.33 .003
BSI (yes/no) laboratory evidence of systemic inflammation. These find-
NonePseudomonas aeruginosa 2.35 0.75e7.36 .241 ings also support our data showing that persistent bacter-
BSI (yes/no) emia is more likely than transient or no bacteremia to be
Multivariate analysisdvariables with P ! .2 included
pBSI (yes/no) 5.97 1.85e17.01 .003 associated with CVAs.
Pseudomonas aeruginosa (yes/no) 4.54 1.1e18.36 .048 Independently from infections, patients with CF-LVADs
Atrial fibrillation (yes/no) 2.92 0.92e8.88 .069 need a fine balance of managing procoagulant tendencies
OR, odds ratio; CI, confidence interval; INR, international normalized (due to factors such as increased platelet activation, shear
ratio; BP, blood pressure; pBSI, persistent blood stream infection. stress, and aortic root stasis) and bleeding tendencies (due
 CVA and Infection in LVAD Patients  Trachtenberg et al 123

Fig. 2. Kaplan-Meier curves. (A) Survival after left ventricular assist device implantation according to groups of persistent bloodstream
infection (BSI), BSI (nonpersistent), and no BSI. Patients with persistent BSI had higher all-cause mortality compared with the other 2
groups-P ! .01. (B) Freedom from stroke. Patients with persistent BSI had a higher incidence of strokes significantly different from those
without BSI; P ! .01.

to factors such as acquired von Willebrand disease, arterio- alter this balance in either direction by activating platelets20
venous malformations, and the use of systemic anticoagula- causing endothelial dysfunction,21 indirectly by the poten-
tion and antiplatelet therapy). Persistent bacteremia can tial for antibiotic and warfarin interactions, or by causing

Fig. 3. (A, D, G) Brain computerized tomography, (B, E, H) digital subtraction arteriography, left vertebral artery injections (lateral projection),
and (C, F, I) 3-dimensional angiographic images of 3 patients with LVAD-related Pseudomonas aeruginosa bloodstream infections who developed
hemorrhagic cerebrovascular accidents in whom ruptured mycotic aneurysms were discovered and were treated with endovascular Onyx embo-
lization. (AeC) 48-year-old woman with left ventricular assist device (LVAD)erelated Pseudomonas aeruginosa bacteremia who developed
acute encephalopathy followed by rapid neurologic deterioration and was found to have a large intraparenchymal hemorrhage in the right posterior
parietal lobe as well as 2 ruptured mycotic pseudoaneurysms of the distal angular branch of the right middle cerebral artery. (D-F) 45-year-old man
with LVAD-related Pseudomonas aeruginosa bacteremia who developed headache and visual changes who was found to have a right parieto-
occipital intraparenchymal hemorrhage and a mycotic aneurysm of the distal posterior temporal branch of the right middle cerebral artery. (G-
I) 47-year-old man with LVAD-related Pseudomonas aeruginosa bacteremia who presented with new-onset seizure and was found to have a small
intraparenchymal hemorrhage in the left posterior temporal lobe and a mycotic aneurysm of a distal left posterior cerebral artery branch.
124 Journal of Cardiac Failure Vol. 21 No. 2 February 2015
sepsis and associated inflammatory states. (eg, dissemi-
nated intravascular coagulopathy). The role of endothelial
function in the interplay between bleeding and thrombosis
in patients with CF-LVADs is largely unknown.
We also report the highest number of reported cases of
the formation of mycotic aneurysms secondary to persistent
bacteremia in patients with HMII (Fig. 3). All 3 of these
patients underwent urgent endovascular repair of their an-
eurysms, but those efforts proved to be futile. The formation
of mycotic aneurysms in patients with recurrent bacteremia
supported by CF-LVADs suggests a unique pathophysi-
ology related to an infected intracardiac device. Similar to
CVA in patients with infective endocarditis, this is likely
related to bacterial seeding and/or embolization involving
the cerebral vasculature which increases risk of bleeding.
Management of HCVA can be challenging, with a very
high mortality rate (49%) in patients with LVADs. In our
study, despite urgent endovascular interventions on patients
with HCVA, all of these patients died as a consequence of
the CVA. Similar outcomes have been reported in other
smaller studies.13 Thus, patients supported with HMII who
develop HCVA associated with BSI have a dismal prognosis
and are unlikely to benefit from neurosurgical interventions.
Pseudomonas aeruginosa was a particularly high-risk or-
ganism in our study, with a strong association with HCVAs.
None of the HCVAs could be explained by other risk factors,
such as BP, anticoagulation regimen, or INR.
Study Limitations
Limitations of our study include the fact that it is a single-
center retrospective study and includes patients with the
HMII only. There have been no direct head-to-head compar-
isons of infectious burdens between the HMII and the
Heartware LVAD device, which is the only other commer-
cially available (as BTT only) long-term CF-LVAD.
Although we would expect that a similar phenomenon exists
with all intracardiac devices, we certainly cannot extrapo-
late our findings to patients on such devices. Another limi-
tation is that blood cultures were ordered at the discretion of
the treating physicians, but the variability of diagnosing
pBSI was probably mitigated by the fact that all patients
were treated by the same infectious disease specialist.
The International Society for Heart and Lung Transplan-
tation (ISHLT) has proposed standard definitions for clas-
sifying infections in LVAD patients whether they are
LVAD-specific, LVAD-related, or non-LVAD infections.22
Given the retrospective nature of the present study, we
did not collect sufficient data to allow definite categoriza-
tion into the ISHLT working definitions. Although this is
a limitation, our intent was not to focus on the exact loca-
tion of the infection but instead on the persistence of the
bacteremia, which is not accounted for in the ISHLT
criteria. Our data show that categorizing our patients as
having persistent or nonpersistent BSI has major implica-
tions for mortality and freedom from stroke. We think
that pBSI, as opposed to non-pBSI, is associated with a
greater inflammatory response regardless of the exact loca-
tion of the infection.
We studied average, trough, and peak INRs over a
4-week period before the CVA and found no difference in
any of these categories when matching with patients
without CVA. One limitation to this strategy is that patients
with infections being on antibiotics could potentially have
fluctuations in INRs between the laboratory drawings.
However, INR was checked weekly per our clinical proto-
col, and we found no evidence to suggest that this occurred.
Therefore, we think that INR was not a contributory factor
for CVAs in our cohort.
Conclusion
We demonstrate that persistent BSI, particularly Pseu-
domonas aeruginosa as the microorganism, significantly
increases the risk of all-cause CVA and all-cause mortal-
ity. Once HCVA develops in patients supported with
HMII in the context of bacteremia, the prognosis is
poor and management options are limited. Patients sup-
ported with HMII CF-LVADs who develop persistent
BSI should be monitored closely, and further studies are
needed to corroborate and explore the mechanisms of
such association.
Disclosures
None.
Acknowledgments
The authors thank Dr Sean M. Barber for his contribution
of images to the paper.
References
1. Kirklin JK, Naftel DC, Kormos RL, Stevenson LW, Pagani FD,
Miller MA, et al. Fifth INTERMACS annual report: risk factor anal-
ysis from more than 6,000 mechanical circulatory support patients. J
Heart Lung Transplant 2013;32:141e56.
2. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW,
Dembitsky W, et al. Long-term use of a left ventricular assist device
for end-stage heart failure. N Engl J Med 2001;345:1435e43.
3. Kirklin JK, Naftel DC, Stevenson LW, Kormos RL, Pagani FD,
Miller MA, et al. INTERMACS database for durable devices for cir-
culatory support: first annual report. J Heart Lung Transpl 2008;27:
1065e72.
4. Holman WL, Pamboukian SV, McGiffin DC, Tallaj JA, Cadeiras M,
Kirklin JK. Device related infections: are we making progress?
J Cardiovasc Surg 2010;25:478e83.
5. Dembitsky WP, Tector AJ, Park S, Moskowitz AJ, Gelijns AC, Ronan NS,
et al. Left ventricular assist device performance with long-term circulatory
support: lessons from the REMATCH trial. Ann Thorac Surg 2004;78:
2123e9; discussion 2129e30.
6. Schaffer JM, Arnaoutakis GJ, Allen JG, Weiss ES, Patel ND,
Russell SD, et al. Bleeding complications and blood product utiliza-
tion with left ventricular assist device implantation. Ann Thorac
Surg 2011;91:740e7; discussion 747e9.
 CVA and Infection in LVAD Patients
7. Elmunzer BJ, Padhya KT, Lewis JJ, Rangnekar AS, Saini SD,
Eswaran SL, et al. Endoscopic findings and clinical outcomes in ven-
tricular assist device recipients with gastrointestinal bleeding. Dig Dis
Sci 2011;56:3241e6.
8. Demirozu ZT, Radovancevic R, Hochman LF, Gregoric ID,
Letsou GV, Kar B, et al. Arteriovenous malformation and gastrointes-
tinal bleeding in patients with the Heartmate II left ventricular assist
device. J Heart Lung Transplant 2011;30:849e53.
9. Macko RF, Ameriso SF, Barndt R, Clough W, Weiner JM, Fisher M.
Precipitants of brain infarction. Roles of preceding infection/inflam-
mation and recent psychological stress. Stroke 1996;27:1999e2004.
10. Syrjanen J, Valtonen VV, Iivanainen M, Kaste M, Huttunen JK.
Preceding infection as an important risk factor for ischaemic brain
infarction in young and middle aged patients. Br Med J (Clin Res
Ed) 1988;296:1156e60.
11. Jones HR Jr, Siekert RG, Geraci JE. Neurologic manifestations of
bacterial endocarditis. Ann Intern Med 1969;71:21e8.
12. Pruitt AA, Rubin RH, Karchmer AW, Duncan GW. Neurologic
complications of bacterial endocarditis. Medicine 1978;57:329e43.
13. Aggarwal A, Gupta A, Kumar S, Baumblatt JA, Pauwaa S,
Gallagher C, et al. Are blood stream infections associated with
an increased risk of hemorrhagic stroke in patients with a left
ventricular assist device? ASAIO J 2012;58:509e13.
14. Nakajima I, Kato TS, Komamura K, Takahashi A, Oda N, Sasaoka T,
et al. Pre- and post-operative risk factors associated with cerebrovas-
cular accidents in patients supported by left ventricular assist deviced
single center’s experience in Japan. Circ J 2011;75:1138e46.
 Trachtenberg et al 125
15. Park KH, Lee YM, Hong HL, Kim T, Park HJ, Park SY, et al. Persis-
tent catheter-related Staphylococcus aureus bacteremia after catheter
removal and initiation of antimicrobial therapy. PLoS One 2012;7:
e46389.
16. Fowler VG Jr, Olsen MK, Corey GR, Woods CW, Cabell CH,
Reller LB, et al. Clinical identifiers of complicated Staphylococcus
aureus bacteremia. Arch Intern Med 2003;163:2066e72.
17. Goldstein DJ, Naftel D, Holman W, Bellumkonda L, Pamboukian SV,
Pagani FD, et al. Continuous-flow devices and percutaneous site infec-
tions: clinical outcomes. J Heart Lung Transpl 2012;31:1151e7.
18. Kato TS, Schulze PC, Yang J, Chan E, Shahzad K, Takayama H, et al.
Pre-operative and post-operative risk factors associated with neuro-
logic complications in patients with advanced heart failure supported
by a left ventricular assist device. J Heart Lung Transplant 2012;31:
1e8.
19. Dalager-Pedersen M, Sogaard M, Schonheyder HC, Nielsen H,
Thomsen RW. Risk for myocardial infarction and stroke after
community-acquired bacteremia: a 20-year population-based cohort
study. Circulation 2014;129:1387e96.
20. Fitzgerald JR, Foster TJ, Cox D. The interaction of bacterial pathogens
with platelets. Nat Rev Microbiol 2006;4:445e57.
21. Grandel U, Grimminger F. Endothelial responses to bacterial toxins
in sepsis. Crit Rev Immunol 2003;23:267e99.
22. Hannan MM, Husain S, Mattner F, Danziger-Isakov L, Drew RJ,
Corey GR, et al. Working formulation for the standardization of
definitions of infections in patients using ventricular assist de-
vices. J Heart Lung Transpl 2011;30:375e84.