Download 2010 Left ventricular assist device management in patients

Left ventricular assist device management in patients chronically
supported for advanced heart failure
Jennifer Cowgera, Matthew A. Romanob, John Stulakb, Francis D. Paganib and
Keith D. Aaronsona
a
Division of Cardiovascular Medicine and bSection of
Cardiac Surgery, University of Michigan Health System,
Ann Arbor, Michigan, USA
Correspondence to Jennifer Cowger, MD, MS,
University of Michigan Cardiovascular Center, 1500 E.
Medical Center Drive, SPC 5853, Ann Arbor,
MI 48109-5853, USA
Tel: +1 734 936 5265;
e-mail: [email protected]
Current Opinion in Cardiology 2011,
26:149–154
Purpose of review
This review summarizes management strategies to reduce morbidity and mortality in
heart failure patients supported chronically with implantable left ventricular assist
devices (LVADs).
Recent findings
As the population of patients supported with long-term LVADs has grown, patient
selection, operative technique, and patient management strategies have been refined,
leading to improved outcomes. This review summarizes recent findings on LVAD
candidate selection, and discusses outpatient strategies to optimize device
performance and heart failure management. It also reviews important device
complications that warrant close outpatient monitoring.
Summary
Managing patients on chronic LVAD support requires regular patient follow-up,
multidisciplinary care teams, and frequent laboratory and echocardiographic
surveillance to ensure optimal outcomes.
Keywords
end-stage heart failure, left ventricular assist device, patient management
Curr Opin Cardiol 26:149–154
ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
0268-4705
Introduction
In 1963, Dr Domingo Liotta at Baylor University College
of Medicine implanted the first left ventricular assist
device (LVAD) for the management of postcardiotomy
shock in a patient who had undergone double valve
surgery [1]. After support on the Liotta-DeBakey LVAD
for 10 days at a flow of 1200 ml/min, the patient recovered
myocardial function. This pivotal experience foreshadowed a new era of heart failure management employing
long-term mechanical circulatory support. With minimal
improvements made over the last 20 years in posttransplant survival (50% at 10 years) [2] and the burdens and
complications of the required posttransplant medical
regimen, it is not unrealistic to envision a future where
mechanical circulatory support is deemed preferable to
transplant by many patients and physicians.
Although still in its infancy in 2011, mechanical circulatory support has already rapidly evolved. LVAD manufacturers have improved device size, fluid dynamics,
durability, and battery life. Patient selection, surgical
technique, and postoperative patient management continue to be refined, reducing the frequency of device
complications, patient morbidity and mortality. In the
destination therapy population, for whom 1-year survival
0268-4705 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
in the medical arm of the REMATCH trial was 25%,
survival of advanced heart failure destination therapy
patients supported with a HeartMate XVE LVAD was
improved to 52% [3]. In the continuous flow device arm of
the HeartMate II Destination Therapy trial, destination
therapy survival was further extended to 68% at 1 year
[4].
While the greatest hazard for mortality with LVAD
therapy will likely always be the early perioperative
period, the cumulative hazard for death on LVAD support has not plateaued in any major trial or registry
analysis to date. Thus, to ensure the best outcomes for
our patients on chronic LVAD support, frequent outpatient follow-up and vigilant device, driveline, and heart
failure management are obligatory. This review will
discuss the important complications faced by patients
on chronic LVAD support and means of reducing the risk
for such complications.
Early postoperative management
The operative period imparts the greatest risk for death
following LVAD implantation. In the second annual
report of the Interagency Registry for Mechanical Circulatory Support (INTERMACS), 3-month mortality for
DOI:10.1097/HCO.0b013e3283438258
150 Heart failure
Figure 1 Survival and hazard for death and survival by device strategy
(a)
Survival after primary LVAD
Intermacs : June 2006 – March 2009
Primary LVAD: n = 1092, deaths = 191
0.20 Deaths/month
% Survival 100
0.18 (hazard)
Survival
80
0.16
0.14
0.12
60
0.10
Month % Survival
3 mo
88%
6 mo
83%
12 mo
74%
24 mo
55%
40
20
0.08
0.06
Hazard
0.04
0.02
0
Event: Death (censored at transplant or recovery)
0
3
6
9
12
15
18
21
0.00
24
Months after device implant
(b)
Device strategy at implant
Intermacs : June 2006 – March 2009
Primary LVAD: n = 1092
% Survival 100
90
BTT = 496, deaths = 54
80
BTC = 458, deaths = 92
70
DT = 100, deaths = 39
60
50
40
Month
3 mo
6 mo
12 mo
30
20
10
0
BTT
91%
90%
84%
BTC
85%
78%
72%
DT
85%
72%
64%
P < 0.0001
Event: Death (censored at transplant or explant recovery)
0
3
6
9
12
15
18
21
24
Months after device implant
(a) Survival and hazard for death after left ventricular assist device (LVAD) implant in INTERMACS. Kaplan–Meier estimates for survival following LVAD
implant in 1092 patients enrolled into INTERMACS are shown. All patients underwent implant of Food and Drug Administration-approved LVADs. At
the bottom, the cumulative hazard for mortality (censoring for transplant or recovery) is also shown. (b) Survival by device strategy following LVAD
implant in INTERMACS. Kaplan–Meier estimates of survival according to intended device strategy [bridge to transplant (BTT), destination therapy
(DT), bridge to candidacy (BTC)] is shown for patients undergoing LVAD implant in INTERMACS. Reproduced with permission from [5 ].
the 1283 patients undergoing primary LVAD implant
between 2006 and 2009 was 12% (Fig. 1a) [5]. Operative
survival was lower in those with advanced age, preoperative cardiogenic shock (requiring vasopressors or preoperative temporary mechanical support), evidence of
right ventricular dysfunction, and those for whom the
intended device strategy was not bridge to transplant
(i.e., destination therapy or bridge to candidacy) (Fig. 1b)
[5]. In other studies, risks for death and morbidity in
the LVAD perioperative period include requirements
for preoperative ventilator support [6,7], high perioperative transfusion requirements and/or coagulopathy
[6,8,9], and the development of renal failure following
LVAD implant [10]. Thus, early LVAD survival relies
on careful patient selection and vigilant perioperative
management.
Left ventricular assist device candidate selection
Patient selection is paramount for success after LVAD
support and this has been the subject of prior review
[11,12]. The Lietz–Miller destination therapy risk score
was developed from 222 individuals undergoing HeartMate XVE implant for destination therapy and may be
useful for distinguishing destination therapy candidates
at high risk for poor outcome on LVAD support [13]. The
validity of this score in the bridge to transplant or ‘less ill’
population, as well as those on more contemporary
devices, warrants investigation.
Perioperative management
Strategies to reduce right ventricular failure, bleeding,
and infection risks are the focus of perioperative LVAD
and patient management. The authors refer readers to a
Left ventricular assist device management Cowger et al. 151
prior review on pre and early postoperative LVAD management strategies to reduce right ventricular failure risks
[14]. In addition to a vigilant intraoperative hemostatic
technique [9], preemptive preoperative assessment of
bleeding and right ventricular failure risk is important
[8,15]. When possible, glycoprotein (GP)2b3a inhibitors
and vitamin K antagonists should be discontinued well in
advance of surgery and international normalized ratios
(INRs) should be normalized. Measures to reduce hepatic congestion (diuresis, inotropes, right ventricular afterload reduction) and improve nutritional status should be
undertaken. At the time of LVAD initiation, optimization
of speeds/flows should be done with transesophageal
echocardiogram guidance to minimize septal shift and,
thereby, right ventricular wall stress. Early postoperative
inotrope administration with close monitoring of cardiopulmonary hemodynamics is often beneficial for right
ventricular support and to assist with management of
mobilized intraoperative fluids.
Reducing complications: management of the
outpatient on long-term left ventricular assist
device support
Important complications following LVAD implant
include infection, stroke, device thrombosis, gastrointestinal bleeding, and recurrent heart failure symptomatology with or without multisystem organ failure [16].
The University of Michigan (UofM) LVAD program’s
strategy is to schedule monthly visits with LVAD patients
until they are 6 months postoperative to allow laboratory,
driveline line and volume status monitoring, LVAD
speed optimization, and frequent patient and caregiver
(re)education. After this point, return visits are extended
to 2–3-month intervals unless complications arise.
Heart failure management after left ventricular assist
device implant
Heart failure management after LVAD implant should
include the application of standard American College
of Cardiology/American Heart Association (ACC/AHA)recommended evidence-based medications for heart
failure – angiotension inhibitors and receptor blockers
(ARB), beta-blockers, and aldosterone antagonists [17].
In addition to offering a few patients the chance for
myocardial recovery while on LVAD support, these
medications work with the LVAD to reduce the activation of the renin–angiotensin–aldosterone system
(RAAS) and sympathetic nervous system (SNS). The
RAAS and SNS not only play critical roles in adverse
myocardial remodeling that may impact long-term left
ventricular and right ventricular performance; they also
drive fluid retention and increase systemic afterload.
Hydralazine and nitrate combination therapy can be
added to the medical regimen of patients who are on
maximal tolerated doses of the above medications,
particularly in the setting of elevated pulmonary vascular
resistance or systemic hypertension.
Finally, studies have shown that ventricular arrhythmias
occur at increased frequency following LVAD implant,
especially in the early postoperative period when normal
repolarization is disrupted by myocardial edema and
inflammation [18,19,20]. In a prospective study of 61
patients with an implantable converter defibrillator
(ICD) in place, 34% of patients supported for a mean
of 365 days had an appropriate device intervention for a
ventricular arrhythmia [19]. Thus, ICD prophylaxis
should be strongly considered in patients undergoing
LVAD support; it is standard practice at our center.
Device management
A discussion of device-specific speed/flow management for
all LVAD models and manufacturers is beyond the scope
of this paper. In general, care strategies aim to set device
speeds/flows to optimize left ventricular preload and afterload while simultaneously avoiding perturbation of right
ventricular wall stress. Continuous flow devices (especially
centrifugal pumps) are very afterload sensitive and tight
blood pressure control (goal mean arterial pressure 60–
90 mmHg) should be achieved to facilitate optimal device
flows and reduce device power consumption.
Echocardiography is a critical tool to guide LVAD speed/
flow optimization. Device settings should allow for
decompression of the left ventricle (LV), leading to a
reduction in left ventricular volumes and/or dimensions
from preimplant measures. With appropriate LVAD
flows/speeds, left ventricular afterload is reduced and,
consequently, mitral regurgitation should be insignificant. The apical four chamber view is useful for visualization of the interventricular septum and the left ventricular inflow cannula. Leftward displacement of the
septum induced by high LVAD inflows should be
avoided due to the impact on right ventricular wall stress
and potential for device-induced suction events. Doppler
interrogation of the inflow cannula should be without
turbulence. Elevated inflow velocities may suggest
device thrombosis.
Finally, there is growing evidence that aortic insufficiency tends to progress with the duration of LVAD
support, potentially due to LVAD-induced shear-stress
damage to the aortic root and the root side of the aortic
valve [21,22]. While the clinical impact of aortic insufficiency on LVAD outcomes is not yet known, it could
lead to ineffective LVAD output through blood recirculation. Thus, aortic insufficiency should be monitored in
patients on LVAD support and device speeds may need
to be adjusted accordingly if clinical heart failure is noted
with aortic insufficiency progression. There is data to
suggest that a fully opening aortic valve may have less of a
152 Heart failure
propensity for developing regurgitation [21]. However,
it is unclear at this time whether optimizing device
speeds to ensure regular valve opening will prevent
the development of aortic insufficiency. A regularly opening valve will reduce the likelihood of leaflet fusion, and
maintenance of normal aortic valve operation is likely
important for those in whom myocardial recovery is
anticipated. The risk of development of aortic root
thrombosis is also lessened in the setting of intermittent
aortic valve opening.
Infection
Until a fully implantable technology is available, infection will remain the biggest obstacle to the success of
truly long-term LVAD support. The hazard for sepsis is
highest in the early postoperative period but never
reaches zero, and infection is associated with a marked
reduction in LVAD survival [16,23,24,25]. In the
REMATCH trial, freedom from sepsis at 1 year in HeartMate XVE-supported patients was 58%, and 1-year survival in those with sepsis was 38% compared with 60% in
those without. Device-related infections without septicemia are also prevalent and offer little better prognosis.
In the 465 patients supported with pulsatile pumps in an
INTERMACS (2006–2008) analysis, the infection rate at
12 months was 1.99 events per patient [24]. In the
HeartMate II Destination Therapy trial, LVAD-related
infections (pump, pump pocket, driveline) occurred at
rates of 0.48 and 0.90 events/patient-year for HeartMate
II and HeartMate XVE devices, respectively [4]. Case
series have demonstrated that 60–70% of patients with a
driveline infection require further surgical intervention,
and 20–35% progress to pump infections requiring either
urgent transplant or pump exchange [25,26]. Correlates of
driveline infection include duration of LVAD support
[26], known driveline trauma [26], and larger body mass
index [27,28]. While studies have suggested that HeartMate XVE devices are associated with higher risk for
driveline infection compared with the HeartMate II
[4,28], a recent report suggests that patient characteristics and implant era may confound the interpretation
of these prior nonadjusted analyses [29]. Further, the
association between driveline infections and pump
pocket infections is anticipated to be much less frequent
with the HeartWare HVAD device, as this intrapericardially positioned device does not have an abdominal
pump pocket.
To reduce infectious complications, patient education on
driveline care and infection warning signs is important.
Education should encompass aseptic driveline cleansing
techniques (which can rarely be performed by the patient
alone) and appropriate driveline fixation using an
abdominal binder and Velcro driveline ‘lead locks’.
Our patients are instructed to wear their binder 24 h a
day due to the risk for driveline disruption during sleep.
Patients should be educated on avoiding activities that
may lead to driveline displacement or bandage soiling.
Antimicrobial prophylaxis administered in the perioperative period is targeted at culprit Gram-positive organisms
(Staphylococcus species) as well as certain Gram-negative
(Pseudomonas, Serratia) and fungal (Candida) pathogens.
The duration of postoperative antimicrobial therapy and
specific regimens administered are heterogeneous across
LVAD institutions. Most will continue oral therapy until
full driveline incorporation, which occurs between 3 and
6 months postoperative. At UofM, we use dual therapy
(doxycycline and a fluoroquinolone) until the driveline is
incorporated and then continue therapy with a single
agent thereafter. For some destination therapy patients
felt to be at high risk for infection, dual therapy may be
continued indefinitely, but there is no evidence-based
data to support either practice.
Balancing bleeding risk with thrombosis and thrombotic
complications
Anticoagulation and antiplatelet therapy are required for
most LVADs due to the potential for in-situ device
thrombus formation and cardioembolic complications.
For the HeartMate II device, rates of device thrombosis
in the major trials were very low (0.02–0.03 events/
patient-year), with rates of ischemic stroke ranging from
0.06 to 0.13 events/patient-year [4,30]. No patient in the
XVE arm of the HeartMate II Destination Therapy trial
had a device thrombosis, and ischemic stroke rates were
0.10 events/patient-year [4]. In the outpatient setting,
close monitoring of INRs, serum lactic acid dehydrogenase, serum free hemoglobin, bilirubin, and hematocrit
levels is important.
INTERMACS defines clinically significant hemolysis as
a serum free hemoglobin more than 40 mg/dl more than
72 h after device implant with other clinical signs [31].
Whether other thresholds or other markers of hemolysis
are more sensitive/specific for predicting adverse events
is unknown.
The low thrombotic event rates discussed above come
at increased risks for bleeding complications, even in
patients on HeartMate XVE support for whom warfarin is
not required. In addition to pharmacologic-induced
bleeding diathesis, LVAD support has been shown to
impact hemostasis. Acquired von Willebrand syndrome
with a reduction in von Willebrand factor (vWF) high
molecular weight multimers has been well characterized
and tends to onset early (as soon as 24 h) after LVAD
support, resolving upon device explant [32,33,34].
Other LVAD-induced changes in the coagulation system
include a reduction in factors XI and XII and an increase
in markers of fibrinolysis [35]. In the major trials,
bleeding requiring blood product transfusion occurred
Left ventricular assist device management Cowger et al. 153
in 42–81% of patients and bleeding requiring surgery
occurred in 15–30% of LVAD patients [3,4,30]. Hemorrhagic stroke rates range from 0.05 to 0.11 events/patientyear [3,4,30]. Of growing concern are complications
from gastrointestinal bleeding. Similarly to Heyde’s
syndrome in aortic stenosis, patients on LVAD support
can develop gastrointestinal arteriovenous malformations
with high propensity for bleeding due to acquired vWF
deficiency. Cohort studies show a cumulative incidence
of gastrointestinal bleeding ranging from 32% (mean
patient follow-up 371 days) to 40% (follow-up unknown)
with a mean time to first bleed of 112 and 87 days,
respectively [32,36]. Angiodysplastic bleeds can occur
anywhere in the gastrointestinal tract, tend to be recurrent, and carry associated burdens of blood transfusion
and allosensitization risk. Compared with pulsatile flow
devices, the risk for angiodysplasia development appears
to be higher in patients supported with continuous flow
LVADs, but further studies are underway [36,37].
Unfortunately, there is no known intervention to prevent
or reduce gastrointestinal bleeding risk.
Patient and family education
Because patient device management is integral to LVAD
success, one of the most important components of outpatient management is education. In addition to the
extensive inpatient education provided after LVAD
implant, re-education in the outpatient arena is key.
Patients and caregivers should receive frequent reviews on
(1) device alarms;
(2) proper battery management: changing batteries, carrying back up batteries, purchasing an electric generator for emergency use;
(3) aseptic driveline care and occlusive bandaging;
(4) driveline fixation: proper positioning and sizing of the
abdominal binder, proper fixation of leads to avoid
fracture, high-risk activities that may increase driveline infection risk;
(5) controller fixation;
(6) signs and symptoms of gastrointestinal bleeding.
intervention, 24–7 access to physicians or physician extenders who specialize in LVAD care is essential for patients
and outside practitioners.
Acknowledgements
Disclosures for Drs Aaronson and Pagani – Both doctors have
relationships with HeartWare (unpaid) and Terumo as members of
Clinical Steering Committees. Dr Aaronson’s interactions with HeartWare and Thoratec are regulated by Conflict Management Plans on file
with the University of Michigan’s Conflict of Interest Board. The other
doctors have nothing to disclose.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
of special interest
of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 173).
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3
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This is the landmark study comparing outcomes with the Heartmate II vs. the XVE
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4
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more than 1,000 primary left ventricular assist device implants. J Heart Lung
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8
9
Conclusion
LVAD therapy offers patients with advanced heart failure
improved survival and quality of life. To ensure that
greatest benefits are gained from LVAD support for the
longest duration necessary, careful heart failure, driveline,
and device management are key. A multidisciplinary
approach to patient care that includes cardiac surgeons,
heart failure specialists, infectious disease consultants, and
social work are vital to the success of an LVAD program
and patient outcomes. Clinic visits should be frequent and
should include patient and caregiver education with frequent attempts at re-education. Due to the complexity of
LVAD management and the present ‘novelty’ of the
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Summary of current data on LVAD candidate risk stratification.
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13 Lietz K, Long JW, Kfoury AG, et al. Outcomes of left ventricular assist device
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14 Romano MA, Cowger J, Aaronson KD, et al. Diagnosis and management of
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16 Pagani FD, Miller LW, Russell SD, et al. Extended mechanical circulatory
support with a continuous-flow rotary left ventricular assist device. J Am Coll
Cardiol 2009; 54:312–321.
This report provides longer-term follow-up of quality of life, infection risk, and
survival of patients supported with a HeartMate II LVAD for the bridge to transplant
indication enrolled into the HeartMate II bridge to transplant trial.
27 Raymond AL, Kfoury AG, Bishop CJ, et al. Obesity and left ventricular assist
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17 Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA
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18 Harding JD, Piacentino V 3rd, Rothman S, et al. Prolonged repolarization after
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19 Oswald H, Schultz-Wildelau C, Gardiwal A, et al. Implantable defibrillator
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This study characterizes the burden of dysrhythmias in LVAD-supported patients.
20 Ziv O, Dizon J, Thosani A, et al. Effects of left ventricular assist device therapy
on ventricular arrhythmias. J Am Coll Cardiol 2005; 45:1428–1434.
21 Cowger J, Pagani FD, Haft JW, et al. The development of aortic insufficiency in
LVAD supported patients. Circ Heart Fail 2010; 3:668–674.
This cohort study characterizes the progression of aortic insufficiency in LVADsupported patients and potential mechanisms behind its development.
22 Pak SW, Uriel N, Takayama H, et al. Prevalence of de novo aortic insufficiency
during long-term support with left ventricular assist devices. J Heart Lung
Transplant 2010; 29:1172–1176.
Cohort study examining the progression of aortic insufficiency in LVAD-supported
patients.
23 Holman WL, Park SJ, Long JW, et al. Infection in permanent circulatory
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mechanical circulatory support devices. J Thorac Cardiovasc Surg 2010;
139:1632.e2–1636.e2.
This study reviews the incidence of device infections and correlates of infection
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25 Topkara VK, Kondareddy S, Malik F, et al. Infectious complications in patients
with left ventricular assist device: etiology and outcomes in the continuousflow era. Ann Thorac Surg 2010; 90:1270–1277.
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31 INTERMACS – Interagency Registry for Mechanically Assisted Circulatory
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continuous-flow mechanical device support contributes to a high prevalence
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Key paper discussing the deficiency of vWF multimers in LVAD-supported patients
and risks of bleeding.
33 Heilmann C, Geisen U, Beyersdorf F, et al. Acquired von Willebrand syndrome
in patients with ventricular assist device or total artificial heart. Thromb
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Another key paper discussing the deficiency of vWF multimers in LVAD-supported
patients and risks of bleeding.
34 Geisen U, Heilmann C, Beyersdorf F, et al. Nonsurgical bleeding in patients
with ventricular assist devices could be explained by acquired von Willebrand
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neuroendocrine system. Artif Organs 2002; 26:902–908.
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