Adjustment following implantation of a left ventricular assist device in patients with CHF, and their partners; a prospective, multi-center observational study (ADJUST-LVAD)

In The Netherlands, the incidence and prevalence of heart failure are rising as
is the case in most other European countries. Overall, there are 200,000
patients with heart failure in The Netherlands and around 25,000
hospitalizations annually with a discharge diagnosis of congestive heart
failure (HF). The diagnosis of HF is largely based upon a careful history and
physical examination and confirmation by a more objective test aimed at the
assessing of the cardiac function.

The development of left ventricular assist devices.
Heart failure severely affects the functional status and quality of life (QoL)
of patients. Since there is a great disparity between the number of patients
listed for heart transplantation and actual transplants performed, many
patients die each year while awaiting heart transplantation. Therefore,
improving the long-term outcomes, including morbidity, mortality and QOL of
patients with CHF has been de underlying goal of decades of research on
mechanical circulatory-support devices. Nowadays, these mechanical
circulatory-support devices are used either as bridge to transplantation or as
permanent destination therapy for people who are ineligible as candidates for
heart transplantation [6]. The use as destination therapy, however, has not yet
been approved in the Netherlands. Historically, patients have been supported by
devices engineered with pulsatile design (i.e. Heartmate IP100, VE, XVE,
Thoratec PVAD/IVAD). Pulsatile devices, however, have limitations that preclude
their practical use for extended mechanical circulatory support. These
limitations include a limited durability, large pump size, requirement for
extensive surgical dissection for implant and audible pump operation. The
development of continuous-flow rotary pump technology represents an innovative
design for a new generation of left ventricular assist devices (LVADs). The
Heartmate II LVAD has an axial flow design, weighs about 375 grams and measures
about 4 cm in diameter. Within the pumps is a rotor that contains a magnet. The
rotor assembly is rotated by the electromotive force generated by the motor.
The rotor propels the blood from the inflow cannula out to the natural
circulation.

The impact of left ventricular assist devices on QoL and functional status.
Because LVADs are increasingly used as bridge to transplant for more extended
periods of time (>3 years), with this trend also likely increasing in the
future, it is important to understand the impact of device therapy on
individuals and the family [6]. There are several trials indicating that the
use of continous flow LVADs as bridge to transplantation or destination therapy
improves the QoL and functional status of a patient suffering from heart
failure. However, little is known about these aspect in patients on long-term
mechanical circulatory support. Of the studies focusing on QoL and health
status outcomes after LVAD implantation, five were on the first generation
pulsatile devices (Heartmate VE/IP) and two on the second generation continuous
flow devices (Heartmate II). Patients were followed from two weeks after
implantation in one study and up to one year after implantation in another. One
of the studies was retrospective and could therefore not draw conclusion about
causality. Further limitations of previous studies were the assessment of QoL
at a single point in time, excluding patients that were to ill resulting in a
possible overestimation of QoL outcomes, the inability to distinguish center
effects from individual variability, and neglecting studying the impact of LVAD
therapy on anxiety and depression. At all assessment times patients reported
significantly better overall QoL, improvement in physical and social
functioning, lower levels of stress, and higher coping ability after LVAD
implantation. However, while the overall QoL of many patients after LVAD
implantations improves, psychological problems often still remain prominent and
unexplained. It is not uncommon that psychological symptoms, such as
depression, anxiety, and posttraumatic stress disorders, are under diagnosed
and may be undertreated in patients with LVADs, which can affect their overall
QoL, functional status and survival [15].

The impact of left ventricular assist devices on survival and mortality.
LVAD therapy is associated with great benefits in patients with heart failure
in comparison to medical therapy. This is reflected in a 1-year survival rate
of 52% for patients with a pulsatile-flow device versus 25% receiving
medical-treatment (p=0.002) and a 2-year survival rate of 23% versus 8%,
respectively (p=0.09). A more recent study showed 1- and 2 year survival
estimates of 68% (95%CI, 60-75) and 58% (95%CI, 49-67), respectively, with the
continuous-flow devices and 55% (95%CI, 42-69) and 24% (95%CI, 1-46) with the
pulsatile-flow device [16]. Within two weeks after LVAD implantation patients
reported to be bothered by their physical dependence on others, insomnia,
fatigue, shortness of breath, weakness and a lack of control over their life.
Most deaths occurred within the first three months and were attributable to
stroke, infection or multiorgan failure. During this period neurological
complications are also frequently recorded, including strokes, transient
ischemic attacks and delirium. As a result concerns have been raised about
functional and neurobehavioral changes during LVAD support which can manifests
themselves by cognitive deficits in attention and impairment in recent and
delayed memory [24].

Importantly, after three months improvements could be detected in New York
Heart Association (NYHA) functional class, patient activity scores and
mobility. Significantly fewer complications and deaths were observed during
late follow-up (6-12 months), with the continuous flow LVADs demonstrated at
least equal efficacy with regard to hemodynamic support, ability to improve
renal and hepatic function and overall patient survival over longer durations
compared to pulsatile devices.

Emotional distress in patients implanted with a left ventricular assist device.
Despite many LVAD patients reporting feelings of sadness, lack of control,
anxiousness and fear after implantation, few studies have focused specifically
on symptoms of anxiety, depression and the role of personality in relation to
LVAD concerns, complications and outcomes. Patients with a more pessimistic
attitude, unsure and worried about the LVAD implantation had more
post-operative difficulties and more pain [4]. These findings are consistent
with the results from other studies on heart failure patients which showed that
personality traits such as negative affectivity and social inhibition (i.e.,
Type-D personality; the tendency to experience increased negative emotions and
emotional non-expression) have a negative influence on patient health status,
perceived disability, and even mortality. This further supports the need to
assess the role of LVAD patients* psychological profile in determining
emotional distress, QoL, and functional status. Knowledge of the role of
psychological factors and their importance relative to clinical factors and
disease severity may help optimize treatment in these patients.

The impact of LVAD implantation on the partner/caregiver of the patient.
In addition to anxiety, depression and personality traits, other factors, such
as social support, loneliness and marital quality may have notable effects on
health outcomes in LVAD patients, and may have a more profound impact than
clinical characteristics, including disease severity. Because the caregiver of
the LVAD patient is usually the patients* partner, the LVAD implantation can
have a tremendous effect on the patient-partner dyad and general family
relationships. The caregiver is expected to be available to the patient 24
hours a day and must undergo extensive training and education by an LVAD
coordinator. For most partners the emotional stress increases when they are
given the responsibility of taking care of the patient at home.

A paucity of studies have examined the QoL and psychological burden of partners
and caregivers. One of these studies used semi structured interviews, the other
reported that 65% had a high overall stress rate, with 82% experiencing
moderate to extreme worry, 61% anxiety and 39% depression. Such distress was
found to have a profound impact, preventing more than 20% of the partners and
caregivers from returning to their normal daily life activities or previous
employment. Most caregivers have mixed feelings consisting of guilt and, hope
and start to realize the severity of the disease and the burden to the family
life. They feel they have no time for themselves, no social life and have to
change their lifestyles. With time caregivers learn to cope with the
responsibility, they are able to adapt to *the new life* and become more
optimistic. Hence, including partners in a study simultaneously with LVAD
patients seems an essential novelty in this research area. Data from the
partners need to be compared to that of LVAD patients to develop a more
comprehensive picture of how LVAD implantation affects the family, and to
understand how stress and coping patterns of LVAD patients and their partners
affect each other.

Primary:
To examine changes in health status (functional status and quality of life) and
emotional distress (i.e. anxiety and depression) over time in patients
following LVAD implantation, focusing on intra-individual changes, with a view
to delineating a profile of high-risk patients with respect to the outcomes.

Secondary:
1. To compare the level of health status and emotional distress in LVAD
patients and their partners and the determinants of health
status and distress in both parties.
2. To examine the potentially moderating role of marital quality, loneliness
and Type D personality on patient distress and health
status.
3. To investigate the determinants (i.e. demographic, clinical and
psychological) of morbidity and mortality in LVAD patients at 2-year
follow-up.

The currents study is a prospective, observational, multi-center study, with a
2-year follow-up period. Psychological assessments will take place at 4 points
in time: T0= baseline (i.e. 2-3 weeks after LVAD implantation during
hospitalization), T1=3 months, T2=6 months, and T3=12 months.

The cardiologist will approach participants for study participation, and will
inform them orally and in writing about the study. If the patient agrees to
participate, the partner will also be approached, and they will both be asked
to sign an informed consent form. In the consent form participants have the
possibility to tick a box indicating that they want to be informed about the
outcomes of the study upon study completion. Subsequently, participants are
handed the first (baseline) booklet of questionnaires.

The first assessment time was chosen based on the following considerations; in
approximately 50% of cases there will not be the possibility to obtain a proper
pre-implantation assessment, due to the patient*s acute critical condition
demanding immediate implantation of an LVAD. Moreover, it is an extremely
emotional and stressful time for both the patient and the partner, and it might
be considered not only unethical to add to this burden but also questionable
whether such assessment would reflect their emotional state or rather
pre-implantation distress. In turn, assessment at this time point would lead to
missings (with respect to non-elective patients) but also potentially study
participation refusal due to patients and partners already being emotionally
strained. Shifting the baseline to 2-3 weeks after LVAD implantation will
ensure that patients are medically stable, that the baseline assessment is
homogeneous across the sample and also hopefully lead to less missing data,
including higher response rate. Based on the article of Grady et al. patients
were quite satisfied with their lives 1 to 2 weeks after LVAD implantation
based on total QoL Index scores. Furthermore, mean symptom distress 2 weeks
after surgery was low in most patients.
The follow-up assessments were based on time points when patients are scheduled
for a visit to the outpatient clinic for a check-up, such as to minimize the
burden to the patients. During these follow-ups blood tests, an
echocardiography and exercise capacity-test will be performed in a standard
manner. Blood samples (WBC count, platelet, Hb, HcT, creatinine, ureum, sodium,
potassium liver enzymes, CRP and NT--proBNP) will be taken every 3-6 months as
part of the standard care. In addition to the 12 month follow-up with
psychological questionnaires, patients will be followed up long term (i.e. 2
years) for heart transplantation, mortality and morbidity.

There is no risk associated with the study. Hence, compensation is not
applicable.